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THE   THYROID 

AND 

PARATHYROID    GLANDS 


RICHARDSON 


Digitized  by  the  Internet  Archive 

in  2010  with  funding  from 

Open  Knowledge  Commons 


http://www.archive.org/details/thyroidparathyroOOrich 


The  Thyroid 


AND 


Parathyroid  Glands 


HUBERT   RICHARDSON,   M.D. 

LATE   PATHOLOGIST   TO   MOUNT    HOPE   RETREAT;     PATHOLOGIST   TO    MARYLAND   ASYLUM    AND 

TRAINING   SCHOOL    FOR    FEEBLE-MINDED    CHILDREN;     DEMONSTRATOR   OF 

PHYSIOLOGIC    CHEMISTRY,   UNIVERSITY    OF    MARYLAND 


WITH  SEVENTY-SEVEN  HALF-TONE   ILLUSTRATIONS  MADE 
FROM  SPECIAL    DRAWINGS  BYE.   P.    WIG  HTM  AN 


PHILADELPHIA 

P.    BLAKISTON'S   SON    &    CO 

IOI2    WALNUT    STREET 
'905 


Copyright  1905,  By  P.  Blakiston's  Son  &  Co 


Press  of 

The  new  Era  Printing  company 

Lancaster,  Pa. 


PREFACE. 

The  work  that  lias  been  done  on  the  thyroid  and  para- 
thyroid glands  within  the  past  ten  or  fifteen  years  has 
contributed  to  medical  literature  one  of  its  most  bril- 
liant chapters.  The  careful  elucidation  of  their  physi- 
ological functions,  the  discovery  of  the  active  principle 
of  the  thyroid  and  its  therapeutic  application,  has -filled 
us  with  wonder  and  surprise.  But  a  few  years  ago  the 
most  advanced  text-books  gave  them  but  a  passing  ref- 
erence and  dismissed  the  whole  subject  with  the  vague 
suggestion  that  the  gland  was  constructed  and  placed  in 
its  position  by  the  Divine  Architect  of  the  human  body 
as  an  ornament  to  the  neck,  like  a  bit  of  molding  in  a 
house  or  a  Doric  finish  to  a  column.  Later  it  was  sup- 
posed to  have  some  relation  to  the  voice,  or  to  regulate 
in  some  compensatory  manner  the  intracranial  blood  sup- 
ply, but  nothing  was  known  of  its  true  function  and  im- 
portance. 

Since  Brown-Sequard  and  Bernard  emphasized  the 
theory  of  an  internal  secretion,  which  brought  upon  the 
former  an  avalanche  of  ridicule,  and  Sir  William  Gull 
and  Murray  followed  in  rapid  succession  with  their  start- 
ling revelations  concerning  the  function  of  this  "terra 
incognita, ' '  it  has  been  my  great  pleasure  to  follow,  with 
enthusiastic  interest,  the  contributions  throwing  new  light 
on  this  subject,  and  apply  to  practical  therapeutics  the 
facts  made  clear  by  these  investigations  and  observations. 
Following  in  rapid  succession  after  the  discovery  of  the 
function  of  the  thyroid  gland  came  the  announcement  that 
certain  conditions  of  a  grave  and  persistent  character 
were  due  to  the  congenital  or  acquired  absence  or  abridg- 


VI  PEEFACE. 

inent  of  the  gland,  and  that  these  were  relieved  by  en- 
grafting a  gland  from  a  healthy  animal  into  the  peri- 
toneum or  other  parts  of  the  body,  or  by  injecting  hypo- 
dermically  a  glycerin  solution  of  the  gland  of  the  sheep, 
and  finally  that  the  same  purpose  could  be  accomplished 
by  the  use  of  the  fresh  gland  per  orem.  Then  came  the 
discovery  that  the  gland  could  be  desiccated  and  used 
as  any  other  drug  with  equal  efficacy  and  with  greater 
accuracy. 

Further  research  soon  developed  the  fact  that  still  other 
conditions,  chiefly  associated  with  arrested,  retarded  or 
perverted  development,  either  of  a  physical  or  psychical 
character,  but  generally  both  constituting  what  the  French 
have  called  "type  Loraine"  have  been  found  to  be  asso- 
ciated with  an  arrested  development  of  the  organ  and 
could  be  relieved  by  the  administration  of  the  dried  gland. 

It  has  been  also  demonstrated  that  certain  functions, 
chiefly  menstruation  and  gestation,  demand  an  extra  ex- 
penditure of  thyroid  secretion,  which,  if  not  supplied, 
leads  to  distinct  symptoms,  which  are  also  relieved  by 
the  administration  of  the  dried  gland. 

Not  resting  here,  earnest  investigations  have  shown 
that  it  is  a  most  potent  oxidizer,  with  all  the  far-reaching 
effects  of  such  an  agent  on  the  animal  economy,  and  that 
it  is  a  blood  pressure  reducer  of  seemingly  a  more  exact 
and  reliable  character  than  any  remedy  heretofore  found 
in  our  materia  medica. 

Developments  are  also  being  rapidly  made  concerning 
other  ductless  glands  and  those  having  an  internal  secre- 
tion that  affect  the  normal  relation  and  balance  of  the 
human  economy.  The  suprarenal  gland  has  become  a 
standard  therapeutic  agent  to  a  less  degree,  but  sufficient 
to  give  promise  of  further  development  in  the  future. 

That  the  therapeutic  applications  of  the  pharmaceutical 
preparations  of  these  glands  are  not  more  extensively 


PEEFACE.  Vll 

availed  of  in  medical  practice  is  due,  no  doubt,  to  the 
fact  that  these  useful  developments  have  not  yet  been 
crystallized  into  the  text-books,  and,  being  scattered 
through  the  medical  literature  of  many  languages,  have 
not  been  made  available  to  the  rank  and  file  of  the  profes- 
sion. Appreciating  the  therapeutic  possibilities  of  the 
animal  glands,  I  often  have  occasion  to  regret  that  the 
brilliant  results  of  the  work  that  is  being  done  along  these 
lines  has  never,  as  far  as  I  know,  been  collected  into  one 
comprehensive  volume,  so  that  it  can  be  availed  of  with- 
out an  amount  of  research  with  the  necessary  access  to 
libraries  that  are  not  within  reach  of  the  average  physi- 
cian. It  was  on  this  account  that  I  urged  Dr.  Richardson 
to  give  to  the  profession  a  compilation  of  the  whole  sub- 
ject, adding  his  personal  observations  and  the  scientific 
researches  he  has  made  in  following  up  the  practical  ap- 
plication, with  analyses  of  the  human  gland  under  various 
conditions  of  mental  and  physical  impairment,  and  also 
by  his  urinalyses  and  blood  examinations,  as  well  as  the 
blood-pressure  tests  of  those  to  whom  it  was  being  ad- 
ministered, especially  among  the  insane  and  degenerates, 
while  pathologist  at  Mount  Hope  Retreat. 

His  capacity  for  research,  his  familiarity  with  the  sev- 
eral languages  in  which  the  best  literature  on  the  subject 
has  been  written,  and  his  general  versatility  render  him, 
in  my  opinion,  most  capable  of  doing  this  work,  and  I 
feel  assured  that  his  book  will  supply  a  need  as  much  felt 
by  the  other  members  of  the  profession  as  by  myself. 
I  am  convinced  that  it  will  be  well  and  thoroughly  done, 
and  I  am  sure  I  can  vouchsafe  it  a  kind  and  generous 
reception. 

CHAS.  G.  HILL,  A.M.,  M.D., 

Professor  of  Nervous  and  Mental  Diseases,  Baltimore 
Medical  College;  Physician-in-Cliief  to  Mount  Hope 
Retreat. 


CONTENTS. 


Chapter    I. 
Historical 1 

Chapter    II. 
Embryology — Anatomy — Histology — The  Parathyroids  ....       8 

Chapter    III. 
Physiology 20 

Chapter    IV. 
Chemistry  of  the  Thyroid  Gland 56 

Chapter   V. 
Goitre  73 

Chapter    VI. 
Surgery  of  the  Thyroid  Gland 100 

Chapter    VII. 
The  Thyroid  in  Infections  Diseases 121 

Chapter   VIII. 
Acute  Thyroiditis 129 

Chapter    IX. 
Syphilis  of  the  Thyroid 139 

Chapter    X. 
Cretinism 144 

Chapter    XL 
Myxedematous  Infantilism 161 

Chapter    XII. 
Myxedema  188 

Chapter    XIII. 
Basedow's  Disease   199 

Chapter    XIV. 

Thyroid  Feeding  in  General  Therapeutics 233 

Bibliography  255 

Index   259 

ix 


LIST   OF   ILLUSTRATIONS. 


1.  The  position  of  the  thyroid  after  removal  of  the  muscles 

(v.  Eiselsberg) 9 

2.  Absence  of  isthmus  (Marshall) 10 

3.  Isthmus  with  large  pyramid  (Marshall) 10 

4.  Double  pyramid  (Marshall) 11 

5.  Absence  of  isthmus  with  pyramid  on  left  side   (Mar- 

shall)      11 

6.  The  thyroid  arteries  (v.  Eiselsberg) 13 

7.  Normal  thyroid  gland 14 

8.  The  position  of  the  parathyroid  glands  (Zuckerkandl)  16 

9.  Normal  parathyroid  gland 18 

10.  Monkey  in  tetanic  attack  after  extirpation  of  thyroid 

(v.  Eiselsberg) 35 

11.  A  four  months  old  kid  whose  thyroid  was  removed  at 

21  days  old  (v.  Eiselsberg) 39 

12.  Control  animal  from  the  same  birth  (v.  Eiselsberg) ...  39 

13.  Lamb,  6  months  old,  the  thyroid  being  removed  on  the 

tenth  day  (v.  Eiselsberg) 41 

14.  Control  animal  (v.  Eiselsberg) 43 

15.  Aorta  of  thyroidectomized  sheep  showing  atheroma  (v. 

Eiselsberg) 44 

16.  Circular  stricture  of  the  trachea  from  goitre  (Demme)  80 

17.  Bayonet-shaped  trachea  from  bilateral  goitre  (Demme)  81 

18.  Showing  the  enlarged  veins  in  goitre  (Wolfler) 82 

19.  Bending    and    narrowing    of    the    trachea    by    goitre 

(Demme)  83 

20.  Goitre  of  accessory  thyroids  (Adjutolo) 84 

21.  Retrosternal  goitre  in  a  deep-seated  thyroid  lobe  (Wuhr- 

man) 85 

22.  Intrathoracic  goitre  (Dittrich) 85 

23.  Follicular,  goitre  (v.  Eiselsberg) 86 

24.  Goitre  marked  by  diffuse  follicular   hypertrophy    (v. 

Mikulicz) 87 

25.  Colloid  goitre  (v.  Bruns) 88 

26.  Follicular  goitre  with  ectasia  of  the  veins  of  the  skin 

(v.  Eiselsberg) 89 

xi 


Xll  LIST    OF    ILLUSTRATIONS. 

27.  Cystic  goitre   (v.  Billroth) 90 

28.  Cystic  goitre  (v.  Brims) 91 

29.  Struma  vasculosa 110 

30.  Adenoma  of  thyroid 110 

31.  Cachexia  strumipriva  in  a  girl  26  years  old  (v.  Bruns)  116 

32.  Congestion  of  the  thyroid 122 

33.  Tuberculosis  of  thyroid 135 

34.  Columnar  celled  carcinoma  of  thyroid  gland 141 

35.  Adeno-carcinoma  of  thyroid  gland 141 

36.  Cretin  with  goitre  (v.  Bruns) 145 

37.  Cretin  with  goitre  (v.  Mikulicz) 146 

38.  Cretin,  22  years  old  (v.  Wagner) 147 

39.  Cretin  (v.  Wagner) 148 

40.  Acute  thyroiditis 150 

41.  Suppurative  struma  of  thyroid  gland 150 

42.  Atrophic  gland  from  a  case  of  myxedema 152 

43.  Myxedematous  gland 153 

44.  45.    A  case  of  sporadic  cretinism  before  and  after  thy- 

roid feeding  (v.  Bruns) 156 

46,  47.    A  case  of  sporadic  cretinism,  aged  6  years,  before 

and  after  6  months'  thyroid  feeding 158 

48.  Cretin,  aged  12  years  (Dr.  Rogers) 160 

49.  Skull  of  cretin  calf 162 

50.  Infantilism,  aged  17  years  (Hertoghe),  before  treatment  166 

51.  Infantilism,  aged  17  years  (Hertoghe),  after  6  months' 

treatment 166 

52.  Infantilism,  aged  17  years  (Hertoghe),  after  1  year's 

treatment 166 

53.  Infantilism,  aged  17  years  (Hertoghe),  after  2  years' 

treatment 166 

54.  Skiagram  of  the  hand  of  a  type  Loraine  17  years  old.  .  168 

55.  Skiagram  of  the  hand  of  normal  child  6  years  old 169 

56.  Skiagram  of  the  hand  of  a  case  of  myxedema  19  years 

old 169 

57.  Skiagram  of  the  hand  of  a  type  Loraine,  16  years  old .  .  170 

58.  Skiagram  of  a  normal  hand  20  years  old 171 

59.  A  case  of  infantilism,  19  years  of  age  (author's  case), 

before  treatment,  height  4  ft.  6^  in.,  weight  76  lbs.  172 

60.  A  case  of  infantilism,  19  years  of  age  (author's  case), 

after  treatment,  height  4  ft.  11  in.,  weight  92  lbs.  172 

61.  Infantilism   simulating   type   Loraine,    aged   21   years 

(Hertoghe),  before  treatment 174 


LIST    OF    ILLUSTRATIONS.  xiii 

62.  Infantilism   simulating   type   Loraine,    aged   21   years 

(Hertoghe),  after  4  months'  treatment 174 

63.  Infantilism   simulating   type   Loraine,    aged   21    years 

( Hertoghe ) ,  after  7  months '  treatment 174 

64.  Normal  boy  17  years 177 

65.  Type  Loraine,  27  years 177 

66.  Myxedematous  infantilism,  18  years 177 

67.  68.    Achondroplasia  (Comby) 181 

69.  Myxedema 184 

70.  Incomplete  myxedema  (Hertoghe),  before  treatment.  .   192 

71.  Incomplete    myxedema    (Hertoghe),    after    6   months' 

treatment 192 

72.  Incomplete  myxedema  (Hertoghe),  before  treatment.  .   193 

73.  Incomplete  myxedema  (Hertoghe),  after  treatment...   193 

74.  Basedow's  disease 200 

75.  Thyroid  gland  in  Basedow's  disease 225 

76,77.    Masked  Basedow's  disease  with  slight  exophthalmos  227 


THE  THYROID  AND 
PARATHYROID  GLANDS. 


CHAPTEE    I. 

HISTORICAL. 


The  use  of  animal  organs  in  medicine  dates  from  very 
early  times.  Plinius  states  that  the  Greeks  and  Romans 
used  the  testicles  of  asses  and  even  the  semen  for  impo- 
tence ;  in  Albania  these  organs  are  used  for  the  same  pur- 
pose today,  and  also  for  amenorrhea.  Paracelsus,  in  the 
sixteenth  century,  recommended  the  spleen  for  the  latter 
condition.  Among  barbarous  and  semi-civilized  peoples, 
as  well  as  among  the  peasantry  in  all  countries,  these  cus- 
toms exist.  The  Chinese  physician  prescribes  dried  mouse 
and  lizard ;  the  native  African  uses  the  liver  of  snakes  both 
internally  and  externally  as  an  antidote  for  snake  bite; 
the  warrior  eats  the  heart  of  the  lion  to  give  him  courage. 
In  Southern  France  snails  are  used  for  indigestion  as  well 
as  a  luxury;  in  Cornwall  and  Devonshire  earthworms 
are  given  for  the  same  purpose.  In  the  materia  medica, 
pepsin,  pancreatin,  ingluvin,  codliver  oil  and  ox  gall  are 
official,  all  of  which  are  animal  extracts  connected  with 
the  digestive  functions,  so  that  the  use  of  other  organs  or 
their  extracts  is  but  a  short  step  in  organotherapy. 

In  recent  times  Brown-Sequard  reawakened  interest  in 
the  subject  by  his  scientific  experiments  of  removing  the 
glands  from  animals  and  observing  the  result. 

He  argued  that  every  gland  of  the  body,  whether  it 
l  l 


2  THE    THYEOID    AND    PAEATHYKOID    GLANDS. 

possessed  an  excretory  duct  or  not,  produced  a  secretion 
which  was  necessary  for  the  well  being  of  the  organism, 
and  that  it  should  be  possible  when  an  organ  ceased  to 
functionate  to  substitute  the  secretion  of  healthy  glands 
either  by  transplantation,  hypodermic  injection  of  the 
extract  or  feeding  by  the  mouth.  His  first  attempt  was 
the  use  of  orchitic  extract,  christened  "  Brown-Sequard 
Elixir,"  for  sterility  or  impaired  virility.  The  remedy 
was  a  failure  and  brought  much  undeserved  ridicule  upon 
its  advocate,  but  his  reputation  as  a  scientist  caused  others 
to  investigate  the  subject,  resulting  in  the  discovery  of 
the  use  of  the  thyroid  gland  in  myxedema,  which  is  one 
of  the  greatest  triumphs  of  medicine  in  the  nineteenth 
century.  Brown-Sequard 's  statements  were  investigated 
by  the  Biological  Society  of  Paris,  and  they  reported  that 
by  the  injection  of  semen  and  orchitic  extract  there  was 
produced  a  marked  increase  in  both  mental  and  physical 
force.  These  experiments  and  the  report  excited  the  pub- 
lic into  a  belief  that  the  elixir  of  life  had  been  discovered, 
and  that  old  age  could  be  rejuvenated,  with  the  natural 
consequence  that  pharmaceutical  preparations  appeared 
on  the  market  with  the  most  extraordinary  advertise- 
ments. Notwithstanding  all  this,  the  foundation  was  laid, 
and  many  workers  have  been  steadily  perfecting  organ- 
otherapy, so  that  two  glands  at  least,  the  thyroid  and  the 
adrenals,  have  taken  a  definite  place  in  medicine. 

There  can  be  no  doubt  that  the  testicles  and  ovaries 
have  a  further  function  than  to  secrete  the  substances 
necessary  for  procreation.  The  effect  of  castration  on  the 
mental  and  physical  condition  is  well  known.  In  those 
castrated  before  puberty,  as  the  "castratos"  of  Italy, 
there  is  an  arrest  of  development,  both  mental  and,  to  a 
certain  extent,  physical ;  the  voice  remains  childish,  while 
their  physical  appearance  and  mannerisms  are  those  of  an 
overgrown  child,  with  a  tendency  to  effeminacy.     Those 


HISTOKICAL.  6 

castrated  after  puberty  are  heavy,  sullen,  suspicious-look- 
ing men,  without  energy  or  ambition,  while  as  a  rule  their 
mentality  is  below  the  average. 

"Whatever  may  be  the  active  agent  in  the  testicles,  the 
absence  of  which  produces  these  results,  it  has  so  far  been 
impossible  to  supply  its  place  by  the  use  of  Brown- 
Sequard  's  extract.  The  experiments  of  Fiirbringer  and 
Pulawski  in  Germany  and  Fere,  Baudin,  BourTee  in 
France  gave  only  negative  results. 

The  Russian  chemist,  Poehl,  after  much  careful  an- 
alysis, extracted  spermin  from  the  testicle.  He  found 
that  the  ovaries,  salivary  glands,  thyroid,  liver,  spleen, 
and  probably  the  brain  substance,  also  contained  spermin 
in  small  quantities,  and  argued  that  this  substance  circu- 
lated in  the  organism  and  was  of  physiological  importance. 
A  vast  amount  of  experimental  work  was  carried  out  by 
Tarchanow  and  others.  They  found  that  the  resistance 
of  the  nerve  centers  was  increased,  so  that  the  convulsions 
of  strychnin  and  tetanus  were  controlled,  and  also  that 
young  dogs  injected  with  spermin  developed  more  quickly 
and  better  than  the  control  animals.  They  summarized 
their  results  by  saying  that  spermin  was  an  energetic 
stimulant  of  the  nervous  system  and  probably  also  of 
other  organs,  and  that  it  increased  the  muscle  force  by 
raising  the  blood  pressure. 

Ovarian  extract  has  several  advocates.  Muret  gives 
four  reasons  for  its  use:  (1)  without  ovaries  there  is  no 
uterine  development  or  menstruation;  (2)  ablation  of 
ovaries  in  young  children  causes  them  to  grow  up  without 
feminine  attributes;  (3)  after  puberty  loss  of  ovaries 
entails  cessation  of  menstruation  and  atrophy  of  genital 
organs;  (4)  osteomalacia  is  sometimes  cured  by  oopho- 
rectomy. The  extract  has  not  come  into  general  use,  but 
there  seems  to  be  considerable  evidence  of  its  value  dur- 
ing the  menopause,  in  some  cases  of  chlorosis  and  in 


4  THE    THYROID    AND    PARATHYROID    GLANDS. 

dysmenorrhea.  At  Mount  Hope  Retreat  it  was  tried  in 
some  nervous  and  mental  cases  said  to  be  the  result  of 
laparotomy  and  in  a  few  other  cases  where  it  was  thought 
genital  trouble  existed  without  any  apparent  beneficial 
results.  In  a  paper  read  before  the  American  Medico- 
Psychological  Society  in  1898,  Dr.  E.  S.  Dewey  stated 
that  operations  on  the  genitourinary  organs  stood  first 
on  the  list  of  surgical  operations  producing  mental  dis- 
turbance. Considering  that  the  most  important  periods 
of  life  are  coincident  with  changes  in  the  genital  organs, 
and  that  the  effect  of  even  such  a  small  defect  as  lacera- 
tion of  the  cervix  will  produce  very  considerable  nervous 
symptoms,  it  does  not  appear  unreasonable  to  suppose 
that  the  normal  functionation  of  the  organs  of  generation 
is  necessary  for  the  health  of  the  organism,  and  that  the 
ovaries  and  testicles  being  secretory  in  their  nature  should 
supply  to  the  system  something  necessary  for  its  well 
being. 

The  thymus  gland  has  been  used  in  many  different  dis- 
eases without  any  very  definite  results.  It  was  first  given 
to  a  patient  suffering  from  Basedow's  disease  in  mistake 
for  thyroid  by  Dr.  Owens.  As  it  produced  an  apparent 
beneficial  effect,  it  was  tried  in  other  cases  with  varying 
results.  Svehla  attempted  to  determine  its  physiological 
effect,  coming  to  the  following  conclusions :  Injection  into 
the  femoral  vein  produced  a  fall  in  blood  pressure,  due  to 
weakening  or  paralysis  of  the  vasoconstrictors,  with  in- 
crease in  the  pulse  rate,  due  to  direct  influence  on  the 
heart;  large  doses  produced  an  excitement,  dyspnea  and 
collapse,  ending  in  death  with  postmortem  evidence  of 
asphyxia. 

Baumann  found  that  the  thymus  contained  iodin  in 
organic  combination,  but  in  much  smaller  quantity  than 
the  thyroid.  As  the  thymus  atrophies  at  puberty  and  its 
persistence  after  that  age  is  pathological,  being  associated 


HISTORICAL.  5 

with  certain  forms  of  epilepsy,  and  with  Basedow's  dis- 
ease it  seems  improbable  that  its  administration  to  the 
adult  will  produce  beneficial  results. 

Splenic  extract  has  not  received  much  attention.  H.  C. 
Wood  reports  three  cases  of  Basedow's  disease  as  being 
benefited  by  it.  It  has  also  been  given  with  benefit  in 
cases  of  melancholia  attonita.  In  leukemia  it  gave  nega- 
tive results.  It  is  on  the  market  as  "eurythrol,"  but  pro- 
duces gastric  pain  and  therefore  does  not  permit  of  con- 
tinuous use. 

Bone  marrow  from  the  ribs  of  young  animals  has  been 
extensively  used  in  anemia  without  producing  satisfactory 
results.  Fraser  reports  its  administration  as  having  in- 
creased the  hemocytes  from  1,869,000  to  3,900,000  and  the 
hemoglobin  from  38  per  cent  to  78  per  cent  in  27  days. 

The  pituitary  body  is  an  organ  which  from  its  ana- 
tomical position  would  appear  to  belong  to  the  central 
nervous  system.  Situated  in  the  sella  turcica,  it  is  pro- 
tected from  injury,  and  from  its  glandular  structure  and 
large  blood  supply  it  should  be  of  importance  to  the  well 
being  of  the  organism.  Physiological  experiments  by  its 
extirpation  have  so  far  given  negative  results,  and,  with 
the  possible  exception  of  akromegaly,  in  which  it  is  usu- 
ally found  enlarged,  it  has  not  been  associated  with  any 
disease.  In  animals  after  thyroidectomy  it  has  been 
found  enlarged  by  Steida,  Hofmeister  and  Grley,  but 
whether  it  is  a  compensatory  hypertrophy  has  not  been 
determined.  The  administration  of  its  extract  has  so  far 
produced  only  negative  results.  Anatomically,  according 
to  Andriesen,  its  function  would  appear  to  be  to  take  up 
oxygen  from  the  blood  stream  and  to  destroy  or  render 
innocuous  the  metabolic  waste  products  of  the  central 
nervous  system.  Chemically  it  contains  iodin,  but  in 
very  small  quantities.  The  last  mentioned  writer  gives 
the  following  as  the  predictable  results  of  its  ablation: 


6  THE    THYKOID    AND    PAEATHYEOID    GLANDS. 

Malassimilation  of  oxygen  by  the  nerve  tissues  with  accu- 
mulation of  waste  products,  thus  bringing  about  a  nutri- 
tional failure  and  death  of  the  central  nervous  system, 
when  the  following  symptoms  would  be  produced,  depres- 
sion and  apathy,  muscular  weakness,  loss  of  coordination 
and  equilibration,  development  of  twitchings  and  irreg- 
ular contractions  of  the  muscles,  a  want  of  sufficient  heat 
production  and  consequent  subnormal  temperature  with 
wasting  of  the  body  tissues. 

Desiccated  brain  and  spinal  cord  have  been  used  with  a 
few  reported  successes  on  the  principle  that  in  certain  dis- 
eases the  chemical  processes  for  the  formation  of  the 
specialized  substances  necessary  for  the  nutrition  and 
functionation  of  the  nervous  system  may  be  interfered 
with,  the  administration  of  the  brain  and  cord  containing 
the  specialized  substances  ready  formed  might  supply  the 
place  of  the  lost  function.  Constantine  Paul,  Babes, 
Gibier,  Dana  and  others  report  cases  of  neurasthenia,  epi- 
lepsy, bulbar  paralysis  and  chorea  as  benefited  by  its  use. 
In  Mount  Hope  a  very  obstinate  case  of  melancholia, 
which  had  resisted  the  usual  treatment,  showed  marked 
improvement  through  its  use,  but  in  several  other  cases 
no  improvement  was  observed. 

The  parotid  gland  has  been  used  in  dysmenorrhea  with 
reports  of  success,  but  the  connection  is  not  apparent. 

Grlycocholate  of  soda  has  been  used  with  success  in  treat- 
ing diseases  of  the  liver,  especially  in  hepatic  colic.  None 
of  the  so-called  cholagogues  of  the  Pharmacopeia  increase 
the  flow  of  bile,  while  experiment  has  shown  conclusively 
that  the  bile  salts  are  the  only  cholagogue  at  our  com- 
mand. As  the  bile  is  an  excretion  of  the  liver  as  well  as 
being  a  necessity  for  the  proper  absorption  of  fats,  it  is 
of  the  utmost  importance  that  the  quantity  should  be  kept 
at  normal.  The  solvent  action  of  the  sodium  glycocholate 
on  cholesterin  and  the  bile  pigments  render  it  of  great 


HISTOBICAL.  7 

service  in  hepatic  colic,  both  as  preventing  the  formation 
of  gall  stones  and  also  as  a  solvent  for  stone  already 
present.  It  seems  from  various  reports  to  be  of  great  nse 
in  torpid  liver,  acting  as  a  purge  for  that  organ ;  also,  in 
some  cases  of  chronic  constipation,  in  malarial  and  post- 
febrile hepatic  insufficiency. 

The  extract  of  the  suprarenal  capsule  has  obtained  a 
permanent  place  in  medicine,  the  active  principle  adre- 
nalin is  used  extensively  in  minor  surgical  operations  as 
a  hemostatic ;  internally  it  raises  the  blood  pressure  and 
stimulates  the  heart. 

Extracts  of  the  prostate  gland,  the  liver,  the  kidney 
and  the  lymphatic  glands  have  all  been  tried  with  nega- 
tive results. 

The  thyroid  gland  has  proved  to  be  of  the  greatest  im- 
portance as  a  regulator  of  the  general  metabolism,  inter- 
ference with  its  function  producing  cretinism,  infantilism, 
myxedema  and  Basedow's  disease,  while  from  its. power- 
ful physiological  action  upon  the  blood-vessels  the  extract 
or  the  dried  gland  is  a  most  valuable  addition  to  the 
Pharmacopeia. 


CHAPTER    II. 

EMBRYOLOGY— ANATOMY— HISTOLOGY— THE 
PARATHYROIDS. 

Embryology.— The  thyroid  gland  is  developed  from  the 
anlages,  one  median  and  two  lateral,  which  unite  to  form 
a  common  differentiation.  The  median  anlage  is  an  in- 
vagination vi  the  floor  of  the  pharynx  between  the  bases 
of  the  second  and  first  bronchial  arches  lying  between  the 
two  parts  of  the  tongne  and  consisting  of  a  small  pouch, 
which  commences  to  expand  laterally  at  a  very  early  age 
to  form  the  median  duct,  the  opening  of  which  upon  the 
tongue  corresponds  to  the  foramen  cecum.  The  duct  itself 
is  known  as  the  ductus  thyroglossus,  which  persists  up  to 
the  eighth  week,  gradually  elongating  as  the  thyroid  and 
tongue  separate.  The  ductus  thyroglossus  is  obliterated, 
but  occasionally  exists  throughout  life  as  the  ductus  lin- 
gualis.*  The  lateral  anlages  are  derived  from  the  ento- 
derm of  the  fourth  gill  clefts ;  the  fourth  entodermal  pouch 
develops  a  ventral  prolongation,  becoming  a  closed  vesicle 
entirely  separated  from  the  pharynx;  the  vesicle  curves 
forward  to  form  round  hollow  buds.  The  union  of  the 
three  anlages  takes  place  about  the  seventh  week.  His 
records  that  in  a  human  embryo  of  the  eighth  week  the 
formation  of  the  hollow  acini  had  begun,  and  that  they 
were  lined  with  epithelial  cells,  the  gland  consisting  of 
two  globes  connected  by  a  narrow  isthmus. 

Anatomy.— The  thyroid  body  is  a  highly  vascular  gland, 
consisting  of  two  lobes,  an  isthmus  and  pyramid,  situated 
between  the  second  and  sixth  tracheal  ring,  covered  an- 
teriorly by  the  sternohyoid,  omohyoid  and  sternothyroid 
muscles,  while  the  sternocleidomastoid  also  overlaps  it. 

8 


ANATOMY. 


The  posterior  surface  is  concave  and  rests  on  the  trachea 
and  larynx,  covering  the  recurrent  laryngeal  nerves.     The 


Fig.  1. — The  position  of  the  thyroid  after  removal  of  the  muscles. 
(v.   Eiselsberg.) 

lateral  lobes  cover  the  carotid  arteries;   are  conical  in 
shape,  extending  from  the  fifth  or  sixth  tracheal  ring  to 


10 


THE    THYROID    AND    PARATHYROID    GLANDS. 


the  side  of  the  thyroid  cartilage  covering  the  inferior 
corners  and  adjacent  portions  of  the  alse.  The  isthmus 
usually  lies  across  the  second  and  third  rings  of  the 
trachea,  but  is  inconstant  in  shape  and  position,  often 
being  entirely  absent.  From  the  isthmus  or  from  the 
adjacent  portions  of  one  of  the  lobes  a  slender  conical 


Fig.  2. — Absence  of  the  isthmus. 
(Marshall.) 


Fig.  3. — Isthmus  with  large  pyramid. 

(Marshall.) 


process  ascends  upward  to  the  hyoid  bone  called  the  pyra- 
mid or  middle  lobe.  Occasionally  it  is  attached  to  the 
hyoid  bone  by  fibrous  or  muscular  tissue,  so  that  it  follows 
the  movements  of  the  vocal  organs.  In  front  the  pre- 
tracheal fascia  extends  from  the  isthmus  and  adjacent 
portions  of  the  lateral  lobes  to  the  front  of  the  cricoid 
cartilage,  the  lower  border  of  the  thyroid  cartilage  form- 
ing a  distinct  anterior  ligament.      Each  lobe  is  further 


AX  ATOMY, 


11 


attached  by  a  firm  band  of  fibrous  tissue,  the  lateral  liga- 
ment, to  the  side  of  the  cricoid  cartilage  and  to  the  first 
two  or  three  rings  of  the  trachea.  Each  lateral  lobe  meas- 
ures about  50  mm.  in  length  by  30  mm.  in  width  by  18  mm. 
in  thickness  at  its  largest  part.  The  isthmus  measures 
nearly  12  mm.  and  from  6  mm.  to  18  mm.  in  thickness. 
The  weight  of  the  gland  varies  very  much  with  age  and 


Fig.  4. — Double  pyramid. 
(Marshall.) 


Fig.     5. — Absence     of     isthmus     with 
pyramid  on  left  side.     (Marshall.) 


in  different  countries.  Virchow  places  it  at  from  30  to  60 
grms. ;  Schaefer  in  England  from  30  to  40  grms.  Wells, 
of  Chicago,  gives  the  average  weight  of  60  glands  removed 
in  that  city  as  22  grms. ;  the  gland  decreases  in  weight  as 
age  advances.  The  average  weight  in  persons  over  45 
years  of  age  in  "Wells'  series  was  only  16  grms.,  while  in 
persons  from  20  to  45  the  average  was  25  grms.  The 
gland  appears  to  be  smaller  in  females  than  in  males, 
increasing  in  size  during  pregnancy  and  menstruation. 


12  THE    THYEOID    AND    PARATHYROID    GLANDS. 

Usually  the  lateral  lobes  are  not  perfectly  symmetrical, 
the  left  being  most  often  the  larger  of  the  two,  while  the 
isthmus  and  pyramid  vary  in  size,  may  be  entirely  absent 
or  fused  into  one  or  other  of  the  lateral  lobes.  The  pyra- 
mid occurs,  according  to  Streekiesen,  in  104  out  of  153 
cases  or  about  68  per  cent.  Marshall  only  found  it  in  24 
out  of  60  cases  or  40  per  cent.  Out  of  the  104  of  Stree- 
kiesen 's  cases  it  was  glandular  up  to  the  hyoid  bone  in  55, 
in  12  it  was  connected  to  the  bone  by  fibrous  tissue,  in  2 
by  muscle.  These  muscular  fasciculi,  which  occasionally 
descend  from  the  hyoid  bone  to  the  gland  or  to  its  pyra- 
mid, are  known  as  the  levator  glandulse  thyroidae.  The 
fibers  are  mostly  derived  from  the  hyoid  muscle,  but  occa- 
sionally are  independent. 

The  arteries  of  the  gland  are  the  superior  thyroid  from 
the  external  carotid,  the  inferior  thyroid  from  the  thyroid 
axis  of  the  subclavian  and  sometimes  the  thyroidea  ima 
from  the  arch  of  the  aorta.  They  are  remarkable  for 
their  anastomoses  and  large  size.  They  terminate  in  a 
capillary  network  upon  the  outside  of  the  acini.  The 
veins  which  are  also  large  form  a  plexus  from  which  the 
superior  middle  and  inferior  thyroid  veins  are  formed  on 
each  side.  The  superior  and  middle  thyroid  veins  open 
into  the  internal  jugular,  the  inferior  veins  form  a  plexus 
in  front  of  the  trachea  and  empty  into  the  innominate 
veins. 

The  lymphatics  of  the  thyroid  body  form  numerous 
large  anastomosing  trunks,  both  at  the  surface  and 
throughout  the  substances  of  the  organ.  They  originate, 
according  to  Frey,  in  the  connective  tissue  which  unites 
the  gland  vesicles,  with  the  cavity  of  which  they  appear 
not  to  be  in  communication.  Hiirthle  has,  by  using  in- 
termittent pressure,  caused  injection  fluid  to  pass  into  the 
vesicles  by  the  lymphatics.  Colloid  substance  is  at  times 
found  in  the  lymphatics  similar  to  that  found  in  the  ves- 


ANATOMY. 


13 


icles,  which  appears  to  pass  between  the  epithelial  cells 
into  the  interstitial  connective  tissue  and  thence  into  the 
lymphatics. 

The  nerves  are  derived  from  the  middle  and  inferior 
cervical  ganglia  of  the  sympathetic  and  accompany  the 
blood  vessels.  Accord- 
ing to  Andriesen  there 
are  no  ganglionic  cells  in 
their  course,  their  branch- 
es extending  close  to  the 
base  of  the  epithelium 
cells. 

Accessory  thyroids  are 
'  common,  being  formed  by 
detachments  of  small  por- 
tions of  the  gland  in  the 
embryonic  stage,  and  by 
division  of  the  pyramidal 
process.  They  may  be 
found  anywhere  between 
the  arch  of  the  aorta  and 
the  hyoid  bone,  some- 
times' even  within  the 
bone  itself. 

Anomalies  are  common, 
either  the  pyramid  or  the 
isthmus  may  be  absent  or 
both,  the  isthmus  occa- 
sionally passes  behind  the 
trachea,  one  lobe  or  both 
may  be  absent.  These 
deviations  from  normal 
are  permitted  by  the  fact  that,  unlike  most  parenchyma- 
tous glands,  the  location  of  its  secreting  structure  bears 
no  relation  to  any  fixed  outlet  or  duct. 


Fig.  6. — The  thyroid  arteries, 
(v.  Eiselsberg.) 


14 


THE    THYROID    AND    PARATHYROID    GLANDS. 


Histology.  — The  texture  of  the  thyroid  gland  is  firm, 
appearing  granular  to  the  naked  eye;  it  is  invested  by  a 
thin  transparent  layer  of  dense  areolar  tissue  which  con- 
nects it  with  the  adjacent  parts,  imperfectly  separating 
its  substance  into  small  lobules  of  irregular  form  and  size. 
When  the  organ  is  cut  into  a  yellow  glossy  fluid,  colloid, 
escapes  from  the  cut  surface.     Imbedded  in  its  substance 

are  multitudes  of  closed  ves- 
icles, which  are  held  together 
in  groups  or  imperfect  lobules 
of  areolar  tissue.  The  wall 
of  each  vesicle  consists  of  a 
simple  layer  of  cubical  or  col- 
umnar epithelial  cells,  which, 
according  to  Langandorff,  are 
of  two  kinds,  viz :  those  which 
are  actually  secreting  the  ma- 
terial contained  in  the  vesicles, 
colloid  cells,  and  other  re- 
serve cells  which  may  take  the  place  of  the  colloid  cells 
or  which  may  become  detached  and  mingle  with  the 
secretion.  Both  Langandorff  and  Hiirthle  agree  in  sta- 
ting that  the  secretion  is  formed  partly  by  exudation  from 
the  cells  and  partly  by  their  complete  transformation  into 
colloid  substance.  Bozzi  describes  three  classes  of  cells, 
chief  cells,  colloid  cells  and  cells  undergoing  retrograde 
metamorphosis.  The  chief  cells  are  the  most  numerous 
and  contain  highly  refractive  bodies  which  he  considers  to 
be  colloid  substance ;  they  also  contain  finer  bodies,  which 
are  probably  incompletely  formed  colloid,  but  Babes  and 
others  state  them  to  be  the  pigment  from  the  destroyed 
red  corpuscles;  fat  globules  and  protoplasm  granules  are 
also  present.  The  cells  appear  not  to  have  a  distinct 
membrane,  but  to  blend  with  one  another,  the  outer  ends 
resting  on  the  basement  membrane.     The  colloid  cells  are 


Fig.  7.— Normal  thyroid  gland. 


THE    PAKATHYKOIDS.  15 

smaller  than  the  chief  cells  and  lie  in  irregular  groups 
between  the  chief  cells  from  which  they  are  probably 
derived;  they  possess  a  nearly  homogeneous  protoplasm 
more  deeply  colored,  not  unlike  the  colloid  substance  in 
appearance ;  they  vary  in  shape,  some  appearing  round  or 
oval,  with  the  protoplasm  almost  destroyed,  its  remains 
collected  around  a  central  mass  which  appears  to  be  colloid 
containing  characteristic  vacuoles,  the  nucleus  being  at 
one  side ;  they  also  group  together  so  as  to  resemble  folli- 
cles; sometimes  free  colloid  is  found  between  the  cells. 
The  cells  showing  retrograde  metamorphosis  have  no  col- 
loid mass,  the  nucleus  loses  its  staining  properties  and 
gradually  becomes  indistinct,  the  granules  are  smaller  and 
the  protoplasm  contains  colloid  in  droplets  not  running 
together  to  form  a  mass ;  these  cells  are  formed  when  the 
follicles  fuse  together  and  seem  to  be  due  to  nutrition 
degeneration. 

Embryonal  rests  are  also  found  mostly  near  the  capsule, 
but  also  scattered  around  in  the  connective  tissue  having 
large  nuclei  with  a  small  amount  of  protoplasm,  they  do 
not  appear  to  develop  when  the  gland  is  partially  removed. 

The  method  of  colloid  formation  has  not  yet  been  set- 
tled. Virchow  was  of  the  opinion  that  it  was  first  formed 
indirectly  by  the  cells  in  so  far  that  the  secreted  mucoid 
fluid  was  changed  into  colloid.  Hiirthle  claimed  to  have 
seen  droplets  of  colloid  in  the  cells,  and  that  the  cells  in- 
creased in  size  on  the  formation  of  the  drops,  concluding 
that  the  colloid  arose  from  the  protoplasm  of  the  cells. 
Langhans,  Langandorfr,  Gutkneckt  and  others  are  of  the 
opinion  that  the  cells  themselves  are  transformed  into 
colloid. 

THE    PAKATHYKOIDS. 

The  parathyroids  consist  of  two  pairs  of  small  glandular 
masses,'  first  described  by  Sandstrom  in  1880,  constant  in 
man  and  other  mammals,  always  lying  in  close  proximity 


16 


THE    THYKOID    AND    PAEATHYEOID    GLANDS. 


to  the  lateral  lobes  of  the  thyroid  body.  They  vary  in 
size  from  3  mm.  to  15  mm.  in  diameter  with  an  average 
of  about  6  mm. ;  are  flattened  and  of  a  reddish  color,  some- 
what like  the  thyroid  itself.  In  structure,  however,  they 
differ  from  the  thyroid  proper,  being  composed  of  solid 
masses  of  epithelial-like  cells,  which  often  appear  to  be 

in  sections,  arranged  in  an- 
astomosing columns  with 
numerous  convoluted  blood 
vessels  between  them.  Con- 
nected with  the  cell  masses 
there  are  frequently  lymph 
follicles,  differing  complete- 
ly from  the  thyroid  and  not 
to  be  confounded  with  the 
accessory  thyroids.  Ac- 
cording to  Grley  they  repre- 
sent embryonic  portions  of 
the  true  gland,  and  if  left 
after  the  removal  of  the  lat- 
ter they  are  able  to  develop 
further  and  take  on  the 
functions  of  the  main  organ. 
It  is  thus  he  accounts  for 
the  failure  to  obtain  in  some 
animals  the  usual  results  of 
thyroidectomy.  This  is, 
however,  denied  by  Edmunds,  although  they  appear 
to  increase  in  size  after  the  operation  and  to  act  vicari- 
ously to  some  extent.  Kohn  states  that  there  is  one 
parathyroid  (outer  epithelial  body)  constantly  present  in 
mammals  on  the  lateral  surface  of  each  lateral  lobe  and 
another  on  each  mesial  surface  (the  inner  epithelial  body). 
Associated  with  these  are  small  bodies  of  adenoid  tissue 
which  have  the  characteristics  of  thymus  gland  including 


Fig.  8. — The  position   of  the  para- 
thyroid, glands.      (Zuckerkandl.) 


THE    PARATHYROIDS.  17 

the  epithelial  rests  or  corpuscles  of  Hassel  and  which  tend 
to  blend  insensibly  with  the  neighboring  interstitial  tissue 
of  the  thyroid.  According  to  Pienant  the  tissue  of  the 
parathyroids  is  similar  in  appearance  and  structure  to  that 
of  the  carotid  glands  and  is  not  embryonic  thyroid  tissue. 
He  states  that  they  take  their  origin  from  the  fourth  inner 
bronchial  cleft  of  the  embryo  from  which  also  part  of  the 
thymus  and  the  lateral  rudiments  of  the  thyroid  are  de- 
rived, whereas  the  main  portion  of  the  thymus  and  the 
carotid  glands  are  derived  from  the  third  cleft. 

The  theory  that  the  parathyroids  are  embryonic  tissue 
is  hardly  tenable,  from  the  fact  that  they  develop  in  chro- 
nological advance  of  the  thyroid.  It  must  also  be  con- 
sidered that  they  resemble  the  suprarenal,  the  anterior 
pituitary  and  the  carotid  glands,  which  must  be  looked 
upon  as  adult  tissue.  In  structure  they  seem  to  be  made 
up  of  entodermal  epithelial  cells,  separated  by  capillaries, 
suggestive  of  the  suprarenal.  This  is  most  noticeable  in 
compensatory  hypertrophy,  but,  as  Edmunds  points  out, 
there  are  no  acini  and  no  secretion  of  colloid  substance. 
Gley  has  recently  taken  up  the  position,  supporting  it  by 
physiological  experiment,  that  the  parathyroids  are  glands 
sni  generis  and  have  a  specific  function  related  to  that  of 
the  thyroid.  Welch  describes  the  parathyroids  as  being 
completely  invested  by  a  fibrous  capsule  and  either  con- 
nected with  the  thyroid  gland  by  a  pedicle  of  fibrous  tissue 
or  situated  within  the  body  of  the  gland,  but  always  com- 
pletely separated  from  it  by  connective  tissue.  From  the 
deep  surface  of  its  fibrous  capsule  irregular  septa  are 
given  off,  dividing  the  gland  into  irregular  lobules. 
Clusters  of  fat  cells  are  generally  present  along  the  course 
of  the  vessels  and  of  the  connective  tissue  septa  within 
the  gland  to  which  the  yellow  tint  is  probably  due. 

The  parathyroids  are  of  epithelial  structure  and  are 
composed  of  two  distinct  kinds  of  cells.  The  principal 
2 


18 


THE    THYROID    AND    PARATHYROID    GLANDS. 


cells  have  a  relatively  small  homogeneous  protoplasmic 
body,  which  takes  on  basic  anilin  dyes  in  varying  degrees 
of  intensity,  and  a  relatively  large  pale  nucleus  with  an 
open  chromatin  network.  They  constitute  the  greater 
part  of  the  gland  tissue.  In  their  arrangement  they  show 
at  least  four  different  types:  (1)  a  continuous  uniform 
cell  mass;  (2)  a  continued  cell  mass,  interrupted  at  fre- 
quent intervals  by  strands  of 
connective  tissue,  so  that  on 
section  the  strands  appear  to 
be  surmounted  by  epithelial 
cells;  (3)  a  series  of  anasto- 
mosing columns  of  cells  in  a 
vascular  fibrous  reticulum,  so 
that  on  section  the  epithelial 
cells  appear  as  discrete  mass- 
es completely  surrounded  by 
vascular  connective  tissue ; 
(4)  groups  of  small  acini, 
each  containing  a  small  mass  of  colloidal  material  in  its 
lumen  and  lined  by  a  single  layer  of  epithelial  cells.  It 
seldom  happens  that  a  parathyroid  is  composed  of  cells  ex- 
clusively arranged  in  one  type.  The  second  kind  of  cell  is 
oxyphilic,  having  relatively  to  the  principal  cells  a  large 
granular  protoplasmic  body,  the  granules  of  which  are 
highly  oxyphilic,  with  a  small  darkly  staining  nucleus  and 
densely  arranged  chromatin.  These  cells  are  not  always 
present.  There  are  three  types  of  disposition:  (1)  a 
uniform  cell  mass,  sharply  defined  from  the  principal  cells 
and  situated  either  deep  in  the  substance  of  the  gland  or 
immediately  beneath  its  capsule;  (2)  a  few  columns  of 
cells  which  gradually  mix  with  the  principal  cells;  (3)  a 
single  acini  lined  with  oxyphilic  cells  containing  a  colloid 
lobule   in   the  lumen.     "Welch   considers   that  the   para- 


Fig.  9. 


-Xormal    Parathyroid 
eland. 


THE    PAEATHYKOIDS.  19 

thyroids  resemble  the  anterior  lobe  of  the  pituitary  body 
more  than  the  suprarenal  and  that  it  is  unlike  thyroid 
tissue ;  that  the  colloid  material  does  not  represent  a  higher 
stage  of  glandular  development,  but  is  rather  retrograding 
or  degenerative  in  its  nature. 


CHAPTER    III. 
PHYSIOLOGY. 

The  early  physiologists  looked  upon  the  thyroid  gland 
as  having  no  essential  function,  probably  from  its  having 
no  duct  by  which  its  secretion  could  be  conveyed  to  the 
general  system,  and  from  its  variable  size,  position  and 
shape,  it  was  stated  to  be  for  the  purpose  of  rounding 
out  the  neck,  as  having  some  connection  with  sleep,  as 
influencing  the  voice,  that  it  acted  as  a  reservoir  for  the 
blood  regulating  the  brain  supply.  The  connection  of  the 
gland  with  the  organs  of  generation  had  very  early  at- 
tracted the  attention  of  the  laity.  In  Southern  Italy  it 
has  long  been  the  custom  for  the  parent  to  measure  the 
circumference  of  the  daughter's  neck  before  and  after 
marriage,  an  increase  in  size  being  considered  as  an  evi- 
dence of  conception. 

It  was  not  till  1859  that  systematic  investigations  as  to 
the  function  of  the  gland  were  commenced.  Schiff  per- 
formed thyroidectomy  on  dogs  and  found  that  they  in- 
variably died,  and  therefore  the  gland  was  necessary  to 
life.  A.  and  J.  Biverdin  described  the  symptoms  pro- 
duced by  thyroidectomy,  Ord  followed  in  1878,  and  then 
Kocher  on  the  same  lines,  stimulating  Schiff  to  further 
experiments.  Schiff  reported  in  1884  that  the  extirpa- 
tion of  the  gland  was  not  only  followed  by  death  to  the 
animal,  but  that  it  also  produced  spasms  and  convulsions, 
which  were  prevented  by  the  implantation  of  the  gland 
under  the  skin  or  in  the  peritoneal  cavity.  These  experi- 
ments were  the  commencement  of  an  enormous  amount 
of  work  by  a  large  number  of  scientists  in  every  country, 

20 


PHYSIOLOGY.  21 

resulting  in  a  number  of  different  theories  as  to  the  physi- 
ology of  the  organ,  many  of  which  have  been  proved  to 
be  erroneous  and  are  now  of  little  interest  except  to  the 
historian. 

The  function  of  the  thyroid  gland  is  said  to  commence 
"in  utero, "  or  soon  after  birth  (Wolfler).  Horsley  con- 
siders that  it  commences  before  birth,  but  is  greatest  dur- 
ing the  period  of  growth,  lessening  as  the  vital  processes 
decline.  He  bases  his  opinion  on  the  decrease  of  the 
secretory  power  of  the  gland  in  phthisis,  in  which  the  col- 
loid substance  gradually  disappears  and  the  epithelial 
cells  pass  into  the  embryonic  state,  from  the  fact  that 
removal  of  the  gland  is  more  fatal  in  young  than  in  older 
animals,  and  that  it  decreases  both  in  size  and  activity  in 
old  age.  Nielsen  is  of  opinion  that  the  gland  is  concerned 
in  the  change  of  mucoid  into  connective  tissue  during  the 
fetal  months. 

The  writer  has  analyzed  the  thyroid  glands  of  several 
children  who  died  immediately  after  birth,  and  also  a  few 
prematurely  born,  and  has  never  been  able  to  find  a  trace 
of  iodin  or  of  the  blood  pressure  reducing  substance.  In 
children  of  two  and  three  weeks  old  who  had  died  of 
cachexia,  no  iodin  was  found.  The  earliest  age  at  which 
he  found  iodin  was  three  months.  There  is  a  remarkable 
difference  between  the  calf  and  the  human  fetus.  In  the 
former  the  thyroid  gland  contains  iodin  in  utero.  As  it 
has  been  shown  that  thyroglobulin  is  excreted  by  the 
mammary  gland,  with  the  milk  in  the  human,  the  child 
receiving  in  this  manner  the  necessary  amount  for  its 
metabolism,  it  seems  possible  that  one  of  the  reasons  why 
the  human  infant  is  so  difficult  to  raise  on  artificial  food  is 
the  absence  of  the  necessary  amount  of  thyroid  secretion 
in  the  artificial  food.  As  the  calf  is  born  with  a  function- 
ating thyroid,  cow's  milk  probably  does  not  contain  the 
amount  of  thyroid  secretion  necessary  for  the  development 
of  the  infant. 


22  THE    THYROID    AND    PARATHYROID    GLANDS. 

The  function  of  the  gland  has  been  studied  chiefly  by 
the  indirect  method  of  observing  the  symptoms  after  re- 
moval of  the  gland  from  animals,  and  some  cases  in  man, 
where  the  operation  was  performed  for  disease.  In  the 
early  experiments  the  importance  of  the  parathyroids  was 
not  recognized,  and  consequently  the  symptoms  were  the 
result  of  the  removal  of  both  thyroid  and  parathyroids, 
which  has  caused  much  confusion,  being  further  compli- 
cated by  the  different  results  obtained  with  different  ani- 
mals—-in  some  instances  as  in  the  rabbit— due  to  the  para- 
thyroids being  some  distance  from  the  thyroid  and  not  be- 
ing removed  in  the  operation  with  the  thyroid.  Ewald 
came  to  the  conclusion  that  birds  survived  the  operation ; 
that  rodents  and  herbivora  generally  survived  with  no 
marked  effects,  and  that  in  aged  dogs  the  symptoms  were 
usually  light.  Reptiles,  young  carnivora,  monkeys  and 
man  invariably  die  after  the  operation  if  it  is  completely 
carried  out.  Horsley,  in  1891,  divided  animals  into  four 
classes:  (1)  birds  and  rodents,  in  whom  no  cachexia  was 
produced;  (2)  ruminants  and  ungulates,  in  whom  the 
symptoms  developed  slowly;  (3)  man  and  monkeys,  in 
whom  the  cachexia  was  certain  but  the  symptoms  mod- 
erate; (4)  carnivorous  animals,  in  whom  the  cachexia  was 
most  severe  and  rapid.  These  results  seemed  to  show 
that  the  food  habits  of  the  animals  had  some  bearing  on 
the  importance  of  the  gland  to  the  system,  viz:  that  car- 
nivora were  the  most  affected,  graminivorous  and  corn 
eating  animals  the  least  affected,  while  the  omnivora  occu- 
pied a  middle  position.  The  later  experiments  of  Hof- 
meister,  de  Quervain,  Grley  and  Edmunds  have  shown  that 
there  is  little  or  no  difference,  provided  that  the  whole 
of  the  thyroid,  accessory  thyroids  and  parathyroids  are 
removed. 

The  symptoms  produced  by  the  extirpation  of  the  gland 
are  of  particular  interest  from  their  resemblance  to  vari- 


PHYSIOLOGY.  23 

ous  observed  pathological  conditions  in  man,  and  have 
been  the  means  of  recognizing  many  obscure  diseases  as 
being  the  resnlt  of  cessation  or  perversion  of  function  of 
the  glands. 

In  dogs,  after  the  removal  of  the  gland,  the  first  most 
noticeable  symptom  is  a  derangement  of  the  functions  of 
the  medulla  oblongata,  consisting  in  vomiting  and  dys- 
phagia. The  efforts  of  vomiting  are  accompanied  by 
salivation,  often  preceding  an  attack  of  convulsions  lasting 
till  the  animal  dies.  The  vomited  matter  consists  of  bile 
and  mucus;  anorexia  is  often  present,  and  when  the  re- 
fusal to  take  food  is  absolute  it  is  a  sure  sign  of  a  rapidly 
fatal  result.  Sometimes  the  animal  preserves  the  appetite 
but  finds  great  difficulty  in  taking  nourishment,  owing  to 
the  continuous  spasmodic  contractions  of  the  masseter  and 
the  fibrillar  contractions  of  the  muscles  of  the  tongue. 
Moreover,  the  dysphagia  usually  present  renders  it  as 
difficult  to  swallow  fluids  as  solids,  and  if  by  chance  any 
food  does  enter  the  stomach  it  is  immediately  rejected, 
with  an  increase  of  convulsive  movements,  the  animal 
finally  ceasing  to  make  any  attempt  to  take  food.  Vomit- 
ing occurs  even  when  the  food  is  carefully  introduced  with 
the  tube.  In  a  few  instances  the  animal  continues  to  eat, 
but  the  food  accumulates  in  the  stomach,  the  abdomen 
becomes  distended  and  the  large  intestine  fails  to  dis- 
charge its  contents.  Trophic  disturbances  may  appear  in 
the  form  of  excoriations,  especially  affecting  the  region 
of  the  articulations  in  the  fore  and  hind  limbs,  which  may 
suppurate,  never  showing  any  inclination  to  heal.  Mus- 
cular paresis  and  partial  paralysis  occur  usually  among 
the  earlier  symptoms,  the  extensors  in  particular  being 
affected,  causing  the  staggering  gait  which  is  usually  very 
marked.  Spasms  are  of  frequent  occurrence,  which,  in 
the  first  instance,  affect  the  masseter  and  temporal  mus- 
cles, but  soon  spread  to  the  muscles  of  the  body,  and  seem 


24  THE    THYROID    AND    PARATHYROID    GLAXDS. 

to  be  the  result  of  discharges  which  take  place  at  regular 
intervals.  This  condition  lasts  for  two  or  three  days, 
when  a  violent  general  convulsion  may  occur,  with  a  tend- 
ency to  tetanus.  At  this  period  the  respiration  is  greatly 
increased,  in  some  cases  being  as  high  as  220  per  minute, 
death  often  supervening  in  one  of  these  convulsions.  Co- 
incident with  increase  of  respiration  comes  increase  of 
temperature,  42.0  degrees  C.  and  even  43.6  degrees  C. 
having  been  observed.  In  the  intervals  between  the  at- 
tacks the  temperature  has  been  observed  to  fall  4  degrees 
below  normal. 

In  1887  Munk  made  the  statement  that  dogs  survived 
operations  which  deprived  them  of  the  functions  of  the 
thyroid  gland,  provided  the  wound  healed  well,  but  if 
swelling  of  an  inflammatory  or  edematous  nature,  or  a 
swelling  dependent  on  hemorrhage  or  upon  accumulations 
of  the  secretions  of  the  wound  occurred,  the  animals  died 
with  characteristic  symptoms.  Munk  performed  the  op- 
eration of  isolation  of  the  gland  by  doubly  ligating  and 
dividing  the  veins  of  the  gland.  He  then  lifted  the  lobes 
out  of  their  capsules  and  completely  severed  them  from 
their  connections  with  the  body  of  the  animal  by  ligation 
of  the  vessels  and  nerves  of  the  hilus,  returning  the  lobes 
to  their  original  position.  Xine  dogs  survived  his  experi- 
ments which  were  repeated  and  confirmed  by  Boginski. 
Halstead  suspecting  that  Munk  had  overlooked  the  acces- 
sory glands  and  also  small  portions  of  the  main  gland, 
went  over  the  same  ground  in  the  most  complete  manner, 
finding  that  his  suspicions  were  correct.  He  found  that 
when  the  gland  was  perfectly  isolated  death  ensued  with 
the  usual  symptoms,  which  varied  somewhat  in  different 
animals,  the  most  regular  being  conjunctivitis,  trismus, 
persistent  erection  of  the  penis,  fibrillary  tremors  of  the 
tongue  and  of  the  muscles  generally.  He  then  experi- 
mented with  partial  isolation,  which  he  brought  about  by 


PHYSIOLOGY.  25 

ligating  all  the  vessels  except  the  thyroid  artery,  which 
supplies  the  upper  lobe  and  the  vein  from  the  lower  lobe. 
The  symptoms  thus  produced  were  not  identical  with 
those  occurring  in  complete  isolation.  The  most  constant 
were  tongue  tremors,  licking  movements,  anemia,  con- 
junctivitis, general  tonic  and  clonic  spasms,  inflammation 
of  gums,  with  occasionally  a  falling  out  of  the  hair,  accom- 
panied with  an  itching  of  the  skin,  producing  an  edema- 
tous appearance  not  unlike  myxedema.  This  latter  symp- 
tom only  occurred  when  the  wound  did  not  heal  by  first 
intention.  He  next  experimented  with  piecemeal  removal 
of  the  gland  and  observed  that  the  same  symptoms  were 
produced,  the  amount  of  gland  removed  in  order  to  pro- 
duce them  varying  in  different  dogs,  probably  on  account 
of  the  size  and  number  of  the  accessory  glands  and  to 
individual  peculiarities,  one  dog  doing  well  and  remaining 
in  good  health  with  only  one-eighteenth  of  the  gland  re- 
maining. During  the  experiment  a  female  who  had  had 
the  left  and  the  lower  third  of  the  right  lobe  removed  was 
impregnated  by  a  healthy  unoperated  dog.  She  gave 
birth  to  eight  puppies,  whose  thyroid  glands  were  at  least 
twelve  times  larger  than  normal.  It  is  remarkable  that 
in  this  case  and  also  in  a  similar  one  that  a  few  hours 
before  whelping  the  symptoms  of  complete  thyroid  de- 
privation manifested  themselves  although  each  animal 
possessed  much  more  thyroid  than  was  actually  required 
for  her  wants.  It  had  previously  been  observed  that 
tetany  had  appeared  previous  to  labor  in  cases  with  con- 
genital thyroid  insufficiency.  These  experiments  have 
been  repeated  recently  with  the  same  result  by  Edmunds 
and  are  suggestive.  It  would  be  interesting  to  observe  if 
an  excessive  secretion  or  administration  of  thyroid  during 
pregnancy  would  not  produce  a  reduced  thyroid  in  the 
produce,  which,  if  it  took  place,  might  account  for  some 
cases  of  sporadic  cretinism. 


26  THE    THYKOID    AND    PAEATHYEOID    GLANDS. 

Horsley  divides  the  symptoms  of  thyroidectomy  into 
those  of  over  action  and  of  want  of  action.  The  first 
symptom  of  over  action  is  fibrillar  muscular  tremor,  re- 
sembling tetany.  The  individual  contractions  of  the 
mnscles  follow  one  another  in  monkeys  at  the  customary 
rate  of  clonus,  viz :  eight  to  ten  per  second.  Summation 
next  occurs,  tetanoid  spasms  follow  and  finally  rigidity 
and  contraction.  Symptoms  of  want  of  action  are  motor 
paralysis  and  anesthesia,  the  toxemic  condition  producing 
functional  neurosis,  epilepsy,  hemiplegia,  etc.  Tissue 
changes  are  also  marked,  emaciation  of  an  acute  form, 
with  mucin  in  the  connective  tissue.  If,  however,  the 
cretinoid  condition  supervenes  there  is  no  increase  of 
mucin,  but  fibroid  changes  occur,  coupled  with  emaciation. 
Virchow  suggests  that  the  edema  characteristic  of  myxe- 
dema is  a  metaplasia  of  the  subcutaneous  fat  into  mucus, 
with  an  increase  of  volume ;  the  skin  becomes  coarse  and 
dry  from  the  absence  of  secretion ;  the  subcutaneous  tissue 
thickened  and  inelastic;  the  hair  falls  out,  becoming  thin 
and  gray.  Disorders  of  temperature  also  occur.  The 
intrinsic  changes,  viz :  the  modifications  which  are  intro- 
duced into  the  normal  heat  balance  ofT  the  subject  after 
elimination  of  the  traumatic  factor,  consist  of  a  rise  of 
from  4  degrees  to  5  degrees  during  the  acme  of  the  mus- 
cular twitching.  The  coincidence  of  this  rise  in  tempera- 
ture with  the  nerve  disturbances  suggests  that  it  may  be 
dependent  on  a  derangement  of  the  heat  controlling  cen- 
ters. Before  death  the  temperature  is  subnormal.  Ex- 
ternal heat  has  a  great  effect  on  the  operated  animal,  ex- 
ternal cold  precipitating  the  symptoms.  Animals  which 
were  apparently  in  good  health  while  kept  in  a  high  tem- 
perature developed  the  characteristic  symptoms  at  once 
on  being  exposed  to  cold. 

The  blood  changes  show  a  connection  between  the  gland 
and  the  blood  metabolism.     Normal! v  the  leucocvtes  are 


PHYSIOLOGY.  27 

present  in  a  greater  proportion  in  the  veins  than  in  the 
arteries  of  the  gland,  and  this  proportion  is  greater  than 
that  fonnd  in  the  veins  of  the  limbs.  After  thyroid- 
ectomy there  is  an  increased  venosity  of  the  blood,  with  a 
great  diminntion  of  the  amonnt  of  oxygen.  This  decrease 
of  oxygen  in  the  arterial  blood  may  be  so  great  as  to  be 
less  than  the  oxygen  in  normal  venous  blood,  a  condition 
which  wonld  account  for  many  of  the  symptoms. 

If  a  portion  of  the  thyroid  gland  be  removed  there  is 
a  compensating  hypertrophy  of  the  remaining  part  which 
undergoes  histological  changes,  the  cubical  cells  become 
columnar,  the  vesicles  become  oblong  or  branched  and  the 
colloid  substance  becomes  more  watery,  changes  which 
are  almost  identical  with  those  found  in  the  gland  in  Base- 
dow's disease.  These  changes  are  not  affected  by  division 
of  the  sympathetic.  SchifT  found,  after  destroying  the 
sympathetic  nerve  fibres  acconrpanying  the  blood  vessels 
to  one  lobe,  that  the  lobe  remained  identical  in  minute 
structure.  Horsley  tried  similar  experiments  with  re- 
spect to  the  recurrent  laryngeal  nerve  with  the  same  re- 
sult. Katzenstein  could  find  no  difference  in  the  two 
lobes  after  stimulating  one  and  not  the  other.  Edmunds 
excised  the  superior  laryngeal  nerve  and  a  considerable 
length  of  the  vasosympathetic  lower  down  on  the  same 
side,  thus  any  secreting  fibres  passing  by  the  recurrent 
laryngeal  nerve  would  be  cut  off.  On  this  side  the  thyroid 
lobe  was  not  touched  or  even  seen.  On  the  other  side  the 
lobe,  together  with  the  parathyroids,  was  excised.  Of  the 
ten  dogs  experimented  upon  three  died  in  one,  two  and 
three  days.  No  symptoms  occurred,  but  death  appeared 
to  be  due  to  the  operation,  as  the  thyroid  lobe  was  found 
to  be  almost  free  from  colloid  and  the  secreting  cells  mul- 
tiplying into  the  vesicles.  Seven  of  the  dogs  lived  longer, 
six  showing  symptoms ;  one,  howerer,  was  operated  on 
again  after  twenty-eight  days  without  having  shown  any 


28  THE    THYEOID    AND    PARATHYROID    GLANDS. 

symptoms.  One  was  allowed  to  live  242  days,  dying  with 
a  thyroidal  symptoms.  Another  was  killed  at  the  end  of 
271  days  suffering  from  severe  symptoms.  The  other 
four  were  operated  on  a  second  time.  The  pathological 
findings  in  these  cases  varied  somewhat.  In  one,  in  which 
the  lobe  was  removed  by  a  second  operation,  the  gland  was 
devoid  of  colloid,  the  cells  multiplying  into  the  cavities  of 
the  vesicles.  In  another,  which  had  well  marked  tremors 
but  recovered,  the  gland  was  found  to  be  much  enlarged, 
weighing  3.5  grins.,  or  about  three  or  four  times  larger 
than  normal.  The  colloid  had  disappeared,  the  increase 
in  size  being  due  to  growth  of  young  tissue  between  the 
vesicles,  the  secreting  cells  were  not  multiplying  into  the 
vesicles.  The  animal  which  lived  242  days,  dying  with 
severe  symptoms,  had  a  normal  gland  and  a  normal  para- 
thyroid. In  the  animal  killed  after  272  days  there  were 
some  normal  vesicles,  but  there  were  also  vesicles  filled 
with  multiplying  cells  from  which  the  colloid  had  wholly 
disappeared. 

Hiirthle  has  experimented  on  the  effect  of  the  stimula- 
tion of  various  nerves  by  the  f aradic  current  on  the  secre- 
tion of  the  gland,  and  has  had  negative  results  from  both 
the  laryngeal  nerves  and  the  vasosympathetic.  On  the 
contrary,  Gr.  A.  Schaefer  found  that  the  cells  of  the  thy- 
roid show  the  same  changes  as  those  of  other  glands  after 
the  injection  of  pilocarpine.  As  pilocarpine  only  pro- 
duces its  effects  by  nerve  stimulation  it  follows  that  the 
secretion  of  the  thyroid  must  be  influenced  by  the  stimula- 
tion of  some  nerve  or  nerves.  Hiirthle  suggests  that  the 
stimulation  of  the  gland  is  due  to  the  presence  of  certain 
unknown  substances  in  the  blood,  and  states  that  tying 
the  gall  duct  in  dogs  produced  homogeneous  globules  in 
the  epithelial  cells  and  lymph  spaces  of  the  gland,  which 
showed  the  same  inclination  to  solidify  and  gave  the  same 
staining  reactions  as  the  follicular  colloid  substance,  prov- 


PHYSIOLOGY.  29 

ing  that  the  passing  of  certain  constituents  of  the  bile 
into  the  blood  produced  increased  secretion  of  the  gland, 
and  that  any  nervous  influence  that  may  exist  is  not  cen- 
tral, but  is  due  to  the  ganglia  either  in  or  in  the  imme- 
diate neighborhood  of  the  gland,  and  further,  that  the 
enlarged  gland  of  Basedow's  disease  is  not  primarily  of 
central  origin. 

Sandstrom  discovered  the  parathyroids  in  1880,  and  in 
1881  Cresswell  Baker  independently  also  observed  the 
glands  but  did  not  recognize  them  in  animals,  describing 
them  as  undeveloped  portions  of  the  thyroid  gland.  In 
1884  Horsley  identified  and  described  the  parathyroids, 
but  they  were  not  thoroughly  studied  till  1892,  when  Gley 
published  a  set  of  papers  recording  his  experiments. 
Under  the  name  of  "glandules  thyroidiennes "  he  de- 
scribed in  the  rabbit  two  glands,  one  on  each  side  of  the 
trachea,  situated  at  some  distance  below  the  thyroid,  so 
that  in  previous  operations  for  thyroidectomy  in  that  ani- 
mal these  glands  had  probably  not  been  removed.  In  the 
dog,  on  the  contrary,  the  corresponding  structures  were 
so  closely  incorporated  with  the  outer  surface  of  the  lat- 
eral thyroid  lobes  that  they  must  have  been  almost,  in- 
variably removed  with  the  thyroid.  On  account  of  these 
different  anatomical  arrangements  he  suggested  the  causes 
for  the  relative  insusceptibility  of  the  rabbit  to  thyroid- 
ectomy; he  removed  both  the  thyroids  and  the  parathy- 
roids from  a  series  of  rabbits  with  the  result  that  in  the 
majority  of  cases  acute  symptoms  and  speedy  death  en- 
sued. Further,  he  found  that  the  removal  of  the  thyroid 
alone,  leaving  the  parathyroids  in  situ,  produced  in  the 
dog  and  the  rabbit  little  or  no  result.  At  the  time  of  these 
experiments  (1892)  the  existence  of  the  internal  para- 
thyroids was  not  known,  and  Gley's  work  only  applies  to 
the  external  parathyroids.  No  really  accurate  knowl- 
edge of  the  position  of  these  glands  was  published  till 


30  THE    THYROID    AND    PARATHYROID    GLANDS. 

1895,  when  Kohn's  elaborate  monograph  on  the  thyroid 
gland  of  the  cat  demonstrated  the  fallacies  underlying  all 
previous  operations.  He  found  that  in  the  cat,  dog,  rab- 
bit, and  probably  in  other  mammalia,  there  were  four 
parathyroids,  and  he  further  showed  conclusively  that 
these  bodies  were  not  thyroids  but  were  independent  spe- 
cific structures,  naming  them  "the  external  and  internal 
epithelial  corpuscles  of  the  thyroid." 

In  1896  Vassali  and  Generali  published  the  result  of 
their  experiments.  They  removed  all  the  four  parathy- 
roids, leaving  the  thyroid  in  situ  in  ten  cats  and  in  nine 
dogs.  Of  the  cats  nine  died  by  the  tenth  day,  while  one 
was  living  at  the  end  of  a  month.  All  the  dogs  died 
within  eight  days,  the  symptoms  in  both  cats  and  dogs 
being  the  same  as  those  previously  recorded  as  the  result 
of  thyroidectomy.  As  a  rule,  however,  conclusive  attacks 
were  absent  or  only  very  slight,  but  on  the  other  hand, 
the  phenomena  of  diminished  nervous  excitability  pre- 
dominated in  the  form  of  paralysis,  which  rapidly  killed 
the  animal.  Rouxeau  performed  on  the  rabbit  what  Vas- 
sali and  Generali  had  done  on  the  dog  and  cat,  viz:  he 
removed  the  four  parathyroids,  leaving  the  thyroid  intact. 
The  results  were  not  uniform,  but  he  concludes  that  re- 
moval of  the  parathyroids  is  much  more  serious  than  re- 
moval of  the  thyroid  alone  in  the  rabbit.  Moussu  comes 
to  the  conclusion  that  the  functions  of  the  thyroid  and 
parathyroids  are  different ;  that  suppression  of  the  thyroid 
produces  only  chronic  symptoms,  while  the  suppression 
of  the  parathyroids  induces  acute  symptoms.  He  also  in- 
duced experimental  cretinism  in  the  dog,  cat,  and  birds 
by  the  removal  of  the  thyroid,  the  parathyroids  being  left 
intact.  Welsh,  after  a  number  of  very  careful  experi- 
ments, comes  to  the  following  conclusions:  (1)  Removal 
of  all  four  parathyroids  in  the  cat  leads  to  acute  and  severe 
symptoms,  with  a  rapidly  fatal  issue,  even  though  the  thy- 


PHYSIOLOGY.  31 

roid  be  retained  practically  uninjured.  (2)  Eemoval  of 
three  parathyroids  does  not  lead  to  death,  but  may  cause 
transient  symptoms  similar  to  those  which  result  from 
removal  of  all  the  glandules;  loss  of  two  parathyroids 
does  not  produce  any  appreciable  result.  (3)  Eemoval 
of  the  thyroid  and  some  of  the  parathyroids  may  lead  to 
death  with  acute  symptoms,  if  only  one  parathyroid  is 
left,  but  may  not  induce  any  obvious  derangement  if  two 
parathyroids  are  retained,  at  least  not  for  several  months. 
(4)  Administration  of  fresh  parathyroid  by  the  mouth  has 
no  effect,  either  in  mitigating  the  symptoms  or  in  averting 
death  after  removal  of  the  thyroid  and  parathyroids  in 
the  cat,  even  though  relatively  enormous  doses  are  given. 
In  1898  Edmunds  published  the  results  of  his  very  elab- 
orate experiments  as  to  the  functions  of  the  parathyroids, 
of  which  the  following  are  the  most  important.  In  two 
dogs  about  one  quarter  of  one  lobe  and  the  external  para- 
thyroids were  left,  the  rest  being  removed.  Neither  of 
these  dogs  showed  any  symptoms  during  the  nine  and 
twenty-six  days  they  were  allowed  to  live.  In  two  other 
dogs  the  upper  part  of  the  thyroid  was  left  on  each  side, 
with  the  addition  that  in  each  a  length  of  the  vasosym- 
pathetic  was  removed  on  one  side.  One  of  the  dogs  suf- 
fered from  tetany,  rigidity  of  the  limbs,  tremors,  emacia- 
tion, and  a  trophic  lesion  of  the  skin,  in  the  second  dog 
the  only  symptom  was  emaciation ;  twenty-nine  days  later 
the  remaining  portion  of  the  gland  was  removed,  the  dog 
dying  with  the  usual  symptoms.  In  eight  dogs  one  ex- 
ternal parathyroid  was  left  and  only  just  sufficient  thyroid 
to  avoid  interference  with  the  blood  supply.  The  dogs 
had  no  symptoms,  except  that  one  of  them  became  thin. 
Three  of  these  dogs  were  subsequently  killed  and  the 
parathyroids  identified  by  microscopical  examination.  In 
the  other  five  it  was  attempted  to  remove  the  parathyroids 
during  life.     In  two  this  was  successfully  accomplished, 


32  THE    THYROID    AND    PARATHYROID    GLANDS. 

with  the  result  that  the  animals  had  the  usual  symptoms. 
In  the  other  three  dogs  the  part  removed  proved  not  to  be 
parathyroids  and  no  symptoms  resulted,  the  parathyroids 
being  found  on  postmortem  examination.  In  seven  other 
dogs  it  was  intended  to  leave  the  external  parathyroids, 
but  microscopical  examination  proved  that  the  tissue  left 
was  not  parathyroid,  all  three  dogs  dying  with  the  usual 
symptoms.  As  dogs  live  when  the  parathyroids  are  left 
and  die  when  it  is  subsequently  removed,  or  when  only  a 
small  piece  of  thyroid  proper  is  left  instead,  it  seems  evi- 
dent that  the  excision  of  the  parathyroids  is  the  cause  of 
the  acute  symptoms,  tremors,  rigidity,  convulsions,  dysp- 
nea and  death,  which  follow  the  total  excision  of  the 
thyroid  and  parathyroids,  and  further  it  suggests  that 
the  excision  of  the  thyroid  proper  only  causes  the  symp- 
toms of  myxedema.  In  four  rabbits,  from  which  the 
thyroid  was  removed,  leaving  the  parathyroids,  the  health 
failed,  the  hair  fell  out,  edema  occurred  in  the  lower  part 
of  the  face,  followed  by  death.  Vassali  and  General! 
have  found  that  if  all  the  four  parathyroids  in  the  dog  are 
excised  and  the  whole  of  the  thyroid  left  the  dog  will  die 
with  the  usual  symptoms  in  a  few  days,  while  if  one  of 
the  parathyroids  is  left  and  the  whole  of  the  thyroid  re- 
moved the  animal  will  live.  Grley  found  that  if  the  whole 
of  the  thyroid  proper  and  one  parathyroid  were  removed 
in  rabbits  the  animal  would  live,  but  if  the  remaining 
parathyroids  were  excised  the  rabbit  would  die  with  the 
usual  symptoms.  In  dogs  in  which  a  single  parathyroid 
was  left  and  a  minute  piece  of  the  thyroid  no  symptoms 
of  any  kind  appeared,  even  after  five  months.  The  ani- 
mals were  kept  so  long  in  order  to  see  if  the  parathyroids 
developed  into  thyroid  tissue.  They  did  not,  but  the  cells 
became  more  definitely  arranged  in  rows,  small  collections 
of  secretion  were  seen  and  the  trabecule  of  connective 
tissue  were  much  thickened. 


PHYSIOLOGY.  33 

In  order  to  obtain  an  obvious  case  of  myxedema,  the 
whole  of  the  thyroid  gland  was  removed  from  four  mon- 
keys. In  the  first  there  was  muscular  weakness,  the  hair 
fell  out  extensively  from  the  front  of  the  chest  and  there 
was  some  swelling  about  the  face,  but  only  temporarily. 
Four  and  a  half  months  after  the  operation  a  well-marked 
edema  occurred  in  the  face  but  quickly  passed  away,  and 
in  six  and  a  half  months  the  monkey  was  well.  The  other 
three  monkeys  died  with  the  usual  symptoms.  The  fail- 
ure to  obtain  true  myxedema  in  these  cases  was  appa- 
rently caused  by  the  animals  dying  from  the  nerve  symp- 
toms before  the  myxedema  had  time  to  develop.  Four 
other  monkeys  were  operated  upon  as  before  and  treated 
with  thyrocolloid,  prepared  according  to  Hutchinson's 
method.  The  first  monkey  died  in  six  days  in  spite  of 
treatment,  and  the  second  had  slight  symptoms  on  the 
first  day  which  passed  off.  On  the  twenty-seventh  day 
the  treatment  was  stopped,  three  days  later  symptoms  ap- 
peared but  passed  off,  when  treatment  was  renewed,  the 
animal,  however,  dying  on  the  forty-first  day.  The  third 
monkey  had  no  symptoms  from  the  first;  the  treatment 
was  stopped  on  the  sixteenth  day ;  on  the  twenty-first  day 
symptoms  appeared,  treatment  was  resumed,  the  symp- 
toms disappeared,  and  five  months  after  the  operation  the 
monkey  was  well.  In  the  fourth  monkey  symptoms  ap- 
peared on  the  third  day  and  the  monkey  died  on  the 
seventh  day  in  spite  of  treatment.  Though  three  out  of 
four  of  the  monkeys  died  yet  treatment  had  some  effect. 
Edmunds  summarizes  the  results  of  his  experiments,  com- 
ing to  the  following  conclusions :  ( 1 )  the  parathyroids  of 
dogs  have  as  much  or  more  to  do  with  saving  them  from 
acute  myxedema  as  the  thyroid  proper;  (2)  although  the 
extract  from  the  thyroids  of  sheep  may  keep  off  and  re- 
lieve the  symptoms  in  thyroidless  monkeys  it  will  not,  as 
a  rule,  save  their  lives;   (3)   a  parathyroid  will  not  by 


34  THE    THYEOID    AXD    PARATHYROID    GLANDS. 

process  of  compensatory  hypertrophy  develop  into  thyroid 
tissue;  (4)  the  mortality  was  44  per  cent  after  total  ex- 
cision of  the  parathyroids,  and  after  excision  of  both  thy- 
roid and  parathyroids  the  mortality  was  80  per  cent,  even 
with  thyroid  feeding;  (5)  the  symptoms  produced  by  the 
excision  of  the  parathyroids  are  the  same  as  by  the  com- 
plete operation  (thyroid  and  parathyroids),  viz:  tremors, 
a  slow  and  unstable  gait,  passing  into  paralysis  of  the 
hind  limbs,  emaciation  and  muscular  weakness. 

The  microscopic  changes  found  in  the  thyroid  lobes  in 
cases  of  excision  of  the  parathyroids  are  marked  in  these 
cases  which  survive  the  operation  a  few  days.  There  is 
a  diminution  in  the  amount  of  colloid  in  the  vesicles,  the 
vesicles  themselves  becoming  oblong  and  branched,  the 
secreting  cells  columnar  or  multiply  so  as  to  fill  the  cavity 
of  the  vesicle  and  there  is  an  excessive  amount  of  young 
thyroid  tissue  between  the  vesicle.  Edmunds  considers 
these  changes  to  be  identical  with  those  described  as  com- 
pensating hypertrophy  of  the  thyroid  and  with  the 
changes  found  in  Basedow's  disease;  there  is,  however, 
an  apparent  decrease  in  the  size  of  the  gland. 

In  two  of  the  dogs,  after  partial  parathyroidectomy, 
there  were  marked  eye  symptoms.  Auld  and  others  have 
noted  eye  symptoms  after  thyroid  feeding,  Beclere  re- 
porting a  case  where  a  patient,  partly  by  mistake,  took  60 
grins,  of  sheep's  thyroid  in  a  week,  which  was  followed 
by  thyroidismus  and  a  certain  amount  of  exophthalmos. 
Edmunds  performed  a  number  of  experiments  to  investi- 
gate the  point,  the  subject  being  of  great  importance  from 
the  possibility  of  its  offering  an  explanation  of  the  pathol- 
ogy of  Basedow's  disease. 

Total  thyroidectomy  was  performed  on  ten  monkeys, 
five  of  whom  had  had  thyroid  feeding  before  the  opera- 
tion. Of  the  five  which  had  no  thyroid  feeding  two 
showed  narrowing  of  palpebral  fissure,  one  at  first  widen- 


PHYSIOLOGY. 


35 


ing,  followed  by  narrowing,  and  in  two  no  change.  Of 
the  five  which  had  thyroid  feeding,  in  two  there  was 
exophthalmos  with  widening  of  the  fissures;  in  one  nar- 
rowing, and  in  two  no  change.  In  another  monkey  no 
operation  was  performed,  but  it  was  fed  with  large  doses 
of  an  extract  equal  to  about  half  a  sheep's  thyroid  per 
diem.  A  considerable  widening  of  the  palpebral  fissures 
resulted,  with  perhaps  some  protrusion  of  the  eyeballs. 
Edmunds,  in  further 
experiments  on  six 
monkeys  fed  with  from 
a  half  to  three  whole 
sheeps '  thyroids  per 
day,  produced  prop- 
tosis,  dilatation  of  the 
pupils,  widening  of  the 
palpebral  fissure,  erec- 
tion of  the  hairs  of  the 
head,  falling  out  of  the 
hair  in  patches,  paral- 
ysis of  one  or  more 
limbs,  emaciation  and 
muscular  weakness, 
followed  by  death  from 
asthma.  The  average 
life  of  the  monkeys 
after    the    commence- 


Fig.   10. — Monkey  in  tetanic  attack  after 
extirpation  of  thyroid,     (v.  Eiselsberg. ) 


ment  of  the  treatment  was  seventy-six  days.  Microscopic 
examination  of  the  thyroids  and  of  pituitary  glands  were 
made,  but  no  pathological  condition  could  be  detected. 
Shortly  before  death  the  animal  showed  an  objection  to 
light  and  to  being  looked  at. 

As  the  effect  of  thyroid  feeding  on  the  eye  might  be 
produced  by  action  on  the  central  nervous  system,  com- 
municating with  the  cervical  sympathetic  or  by  local  action 


36  THE    THYROID    AND    PARATHYROID    GLANDS. 

on  the  ganglia  in  and  about  the  eye,  the  cervical  sympa- 
thetic was  divided  on  one  side  in  two  monkeys  and  the 
animals  fed  in  doses  corresponding  to  about  three  sheeps' 
thyroids  per  day.  In  twelve  days  the  eyes  on  the  unop- 
erated  side  were  seen  to  be  more  prominent  and  the  palpe- 
bral fissure  wider  than  before  treatment;  the  eyes  on  the 
operated  side  also  became  very  wide  and  prominent.  A 
considerable  length  of  the  nerve  was  removed  to  prevent 
the  probability  of  repair.  This  experiment  is  borne  out 
by  a  case  reported  by  Boissou.  The  patient,  a  girl  of 
twenty  years  old,  was  submitted  to  resection  of  the  cer- 
vical sympathetics,  first  on  one  side  and  then  on  the  other, 
for  Basedow's  disease.  Notwithstanding  the  operation 
the  exophthalmos  continued  and  became  so  severe  that  the 
eyes  could  not  be  closed,  the  cornea  sloughed,  sight  was 
lost,  the  patient  dying  in  a  short  time. 

This  case  and  Edmunds'  experiments  show  that  the 
cervical  sympathetic  is  not  the  main  factor  in  producing 
the  protrusion  of  the  eyeballs,  and  it  also  seems  probable 
that  thyroid  extract  acts  partly  through  the  cervical  sym- 
pathetic and  partly  locally.  Experiments  were  also  made 
on  rabbits,  with  the  thyroid  with  the  two  smaller  parathy- 
roids removed.  In  one  rabbit  the  eyes  became  more  promi- 
nent and  remained  so ;  in  one  no  change  was  observed  for 
nine  months,  when  the  eyes  began  to  get  narrow,  becoming 
very  narrow  before  death.  The  cervical  sympathetic  was 
excised  on  both  sides  to  see  if  it  produced  further  narrow- 
ing; in  two  the  eyes  became  very  narrow  before  the  ani- 
mals died,  which  occurred  in  two  or  three  days ;  in  three 
the  eyes  narrowed  and  the  animals  lived,  and  in  one  there 
was  no  change.  The  thyroids  of  the  four  surviving  rab- 
bits were  excised,  the  two  larger  parathyroids  being  left 
intact.  In  one  there  was  a  marked  increase  in  the  nar- 
rowing, in  the  other  two  no  immediate  effect,  but  the  ani- 
mals died  ten  months  later  with  very  narrow  eyes.     In  the 


PHYSIOLOGY.  37 

rabbit  in  which  division  of  the  sympathetic  had  produced 
no  symptom,  the  excision  of  the  thyroid  was  followed  by 
death  in  three  days  with  narrow  eyes. 

In  further  experiments  to  observe  the  effect  of  the  ex- 
cision of  the  parathyroid  on  the  eye,  Edmunds  excised 
both  cervical  sympathetica  in  a  rabbit,  which  caused  nar- 
rowing of  the  palpebral  fissures ;  later  he  excised  the  thy- 
roid together  with  the  two  smaller  parathyroids,  leaving 
the  two  large  parathyroids.      This  operation  produced  no 
further  narrowing.     In  five  rabbits  he  excised  the  two 
larger  parathyroids,  leaving  the  thyroid  intact,  together 
with  the  two  smaller  parathyroids.     In  four  animals  the 
eyes  became  somewhat  wider  for  a  time,  reverting  to  nor- 
mal :  in  one  there  was  no  change.     In  six  rabbits  the  op- 
posite operation  was  performed,  namely,  the  two  larger 
parathyroids  were  left  intact  and  the  thyroid  lobes  with 
the  two  smaller  parathyroids  were  excised.      The  results 
varied,  in  three  of  the  rabbits  it  was  noticed  that  the  eyes 
for  a  time  were  wider  than  normal,  four  of  the  rabbits  died 
and,  at  the  time  of  death,  their  eyes  were  much  narrowed ; 
two  were  killed  at  a  time  when  the  eyes  were  normal. 
Edmunds  summarizes  his  results  as  follows : 

(1)  That  after  complete  excision  of  the  thyroid  and 
parathyroids  the  great  majority  of  dogs  die  within  a  few 
days  and  cannot  be  saved  by  thyroid  feeding,  but  a  small 
minority  survive  even  after  the  complete  operation. 

(2)  In  operations  in  which  one  or  more  parathyroids 
are  left  the  dogs  as  a  rule  survive. 

(3)  That  when  only  the  thyroid  is  left  they  die  as  a  rule. 

(4)  That  with  respect  to  operations  that  paralyze  the 
secretory  nerves  of  the  thyroid  the  dogs  often  die,  al- 
though possessed  of  the  whole  of  one  thyroid  lobe,  to- 
gether with  the  parathyroids  of  'the  same  side,  or  even  as 
in  Halstead's  experiments  when  possessed  of  the  whole 
thyroid. 


38  THE    THYROID    AND    PAEATHYEOID    GLANDS. 

(5)  With  respect  to  the  microscopical  appearances  of 
the  parts  left  in  the  experiments,  the  parathyroids  seem 
merely  to  hypertrophy,  and  they  do  not  change  into  thy- 
roid tissue  proper.  The  thyroid  tissne  may  remain  un- 
altered even  though  the  dog  may  die  of  athyroidic  symp- 
toms, or  it  may  materially  alter  and  this  in  one  or  two 
days ;  either  the  colloid  diminishes  or  entirely  disappears, 
vesicles  enlarge  and  the  lining  membrane  becomes  con- 
voluted. This  may  occur  to  such  a  degree  as  to  present 
appearances  closely  resembling,  if  not  identical  with, 
those  in  a  papilloma,  or  the  colloid  may  disappear,  the 
vesicles  may  retain  their  shape  and  the  round  cells  may 
multiply  into  and  fill  the  cavity  of  the  vesicles,  thus  pro- 
ducing an  appearance  somewhat  similar  to  that  seen  in 
carcinoma,  but  though  much  hypertrophy  sometimes  oc- 
curs nothing  of  the  nature  of  invasion  has  been  seen. 

(6)  In  the  central  nervous  system  changes  have  been 
found  corresponding  to  paralytic  symptoms,  the  lesions 
that  occur  are  observed  mainly  in  the  large  cells,  varying 
from  chromatolysis  of  the  Nissl  granules  to  a  complete 
destruction  of  the  cells. 

(7)  In  the  eyes  of  monkeys,  dogs  and  rabbits  he  finds 
that  when  an  animal  is  dying  of  athyroidic  symptoms, 
whether  after  a  complete  or  only  partial  extirpation,  there 
is,  as  a  rule,  narrowing  of  the  palpebral  fissures.  After 
the  removal  of  the  parathyroids  a  condition  of  widening 
of  the  eyes  occurs,  which  coincides  with  the  view  that 
Basedow's  disease  is  connected  with  the  parathyroids. 

Moussu  has  experimented  with  the  parathyroids  and 
comes  to  the  conclusion  that  the  acute  convulsive  attacks 
in  thyroidectomized  animals  are  due  to  the  parathyroids 
having  been  removed,  and  that  if  operated  dogs  are  given 
the  watery  extract  of  from  twelve  to  twenty  horses '  para- 
thyroids the  convulsions  are  arrested.  He  further  states 
that  myxedema  is  not  helped  by  the  administration  of 


PHYSIOLOGY. 


39 


parathyroid  (confirmed  by  Ckarrin),  but  that  he  has  seen 
improvement  in  a  case  of  Basedow's  disease  by  the  injec- 
tion of  the  extract  of  eight  horses '  parathyroids  per  diem. 
He  sums  up  that  the  removal  of  the  thyroid,  leaving  the 
parathyroids  produces  myxedema  in  man  and  perhaps 


Fig.   11.— A  4  months  old  kid  whose  thyroid  was  removed  at  21  days 

old.      (v.  Eiselsberg.) 
Fig.  12.— Control  animal  from  the  same  birth,      (v.  Eiselsberg.) 

also  in  swine  and  dogs;  in  other  species  progressive  ca- 
chexia. In  the  young  of  man,  swine,  goats,  dogs,  cats  and 
birds  it  produces  cretinism,  which  is  improved  by  the 
administration  of  thyroid.  That  the  removal  of  the  para- 
thyroids in  carnivora  produces  death,  which  was  formerly 
attributed  to  the  absence  of  the  thyroid,  and  that  the  par- 


40  THE    THYROID    AND    PARATHYROID    GLANDS. 

tial  removal  of  the  parathyroids  produces  symptoms  sim- 
ilar to  Basedow's  disease,  it  has  not  been  shown  as  yet 
that  the  parathyroids  are  diseased  in  Basedow's  disease, 
nor  that  feeding  with  parathyroids  will  benefit  the  patient. 
A  few  cases  are  recorded,  but  as  yet  the  benefit  of  the 
treatment  must  be  regarded  as  "not  proven." 

There  seems  to  be  no  doubt  that  the  two  sets  of  glands 
are  not  wholly  independent,  for  the  removal  of  the  thy- 
roids causes  changes  in  the  parathyroids,  and  the  excision 
of  the  parathyroids  changes  in  the  thyroid.  One  very 
attractive  theory  suggests  itself,  that  the  symptoms  of 
myxedema  are  due  to  the  failure  or  removal  of  the  thyroid, 
while  removal  or  failure  of  the  parathyroids  produces  the 
tremors  and  other  nervous  symptoms,  with  the  general 
symptoms  of  Basedow's  disease.  If  the  failure  of  the 
parathyroids  causes  hypertrophic  changes  in  the  thyroid, 
as  shown  by  Edmunds,  it  may  be  supposed  that  the  in- 
creased secretion  of  the  altered  thyroid  would  cause  ex- 
ophthalmos, and  thus  we  should  have,  as  in  Basedow's 
disease,  tremors,  exophthalmos,  etc.  Edmunds  states  that 
excision  of  the  parathyroids  produces  sometimes  exoph- 
thalmos, sometimes  enophthalmos,  and  exophthalmos  can 
be  converted  into  enophthalmos  by  the  removal  of  the 
thyroid  lobes.  Total  thyroidectomy  in  the  monkey  is 
usually  followed  by  enophthalmos,  exceptionally  exoph- 
thalmos, while  thyroid  feeding  produces  exophthalmos  in 
monkeys,  as  a  rule. 

Prof.  Freiherr  v.  Eiselsberg  experimented  with  the  re- 
moval of  the  thyroid  in  young  animals.  He  removed  the 
thyroid  from  two  lambs  at  ten  days  old,  keeping  another 
as  control.  In  a  month  the  control  animal  was  much 
larger  than  the  operated  lambs,  and  at  six  months  the 
control  animal  was  as  heavy  as  both  the  other  operated 
lambs  together.  It  weighed  35  kg.,  compared  with  10  kg. 
and  14  kg.     Not  only  was  the  physical  growth  arrested, 


PHYSIOLOGY.  41 

but  the  mental  condition  was  very  evidently  defective,  and 
there  was  also  a  want  of  coordination.  At  the  autopsy 
there  was  calcification  of  the  aorta,  which  had  the  appear- 
ance of  being  due  to  senile  changes  and  not  to  inflamma- 
tion. He  operated  on  young  goats,  pigs,  rabbits  and  asses 
and  found  the  same  results,  namely,  arrest  of  physical  and 
mental  development,  comparable  to  cretinism. 


Fig.  13.— Lamb,  6  months  old,  the  thyroid  being  removed  on  the 
tenth  day.      (v.  Eiselsberg.) 

The  influence  of  the  thyroid  secretion  on  the  morphol- 
ogy of  the  organs  of  generation  in  both  sexes  has  been 
demonstrated  by  many  observers.  It  is  an  ancient  tradi- 
tion that  the  thyroid  enlarges  at  the  first  menstruation,  in 
certain  women,  each  period  producing  an  appreciable  en- 
largement of  the  gland.  There  seems  also  to  be  a  bal- 
ancing as  it  were  between  the  flow  of  blood  and  the  gland. 
A  suppression  of  menstruation  often  produces  a  swelling 
of  the  gland,  which  disappears  on  the  reestablishment  of 
the  flow.  There  is  also  a  very  remarkable  connection 
pointed  out  by  Gautier  that  the  menstrual  blood  contains 


42  THE    THYROID    AND    PAEATHYEOID    GLANDS. 

iodin  and  arsenic,  both  of  which  substances  are  a  part  of 
the  normal  secretion  of  the  thyroid.  In  girls  it  has  often 
been  stated  that  the  first  sexual  act  produces  an  enlarge- 
ment of  the  gland.  There  seems  to  be  no  connection  be- 
tween the  thyroid  and  the  sexual  act  in  the  male,  it  having 
never  been  observed  to  swell  after  the  first  coitus  but  en- 
larges about  the  time  of  puberty  and  occasionally  a  pal- 
pable goitre  may  form.  The  enlargement  of  the  gland 
during  the  rut  has  been  observed  in  the  dog,  cat,  rat,  sheep 
and  deer,  and  was  described  by  Wagner  in  1858. 

The  effect  of  the  thyroid,  development  on  puberty  is  of 
great  importance.  Broca  ("  Goitre  and  Cretinism, ' '  1891) 
states  that  in  the  complete  cretin  puberty  is  never  estab- 
lished. The  reproductive  functions  are  nil  and  sterility  is 
absolute,  while  arrested  development  of  the  sexual  organs 
is  almost  a  constant  symptom  of  infantilism.  Occasion- 
ally there  are  cases  of  hyperthyroidea  occurring  at  pu- 
berty, which  Brissaud  explains  as  a  result  of  a  difficult 
sexual  metamorphosis,  or,  in  other  words,  that  an  arrested 
development  of  the  sexual  organs  may  produce  thyroid 
derangements.  In  cretinism,  and  especially  in  infantil- 
ism, the  increase  in  the  development  of  the  sexual  organs 
under  thyroid  treatment  is  very  marked.  It  is  of  im- 
portance, from  a  therapeutic  standpoint,  to  note  that  the 
increase  in  size  of  the  thyroid  gland  is  anterior  to  the 
development  of  the  sexual  organs,  the  secretion  of  the 
gland  being  increased,  the  surplus  is  utilized  to  stimulate 
growth,  and,  therefore,  if  the  gland  does  not  increase, 
puberty  does  not  occur  and  the  growth  is  retarded,  pro- 
ducing infantilism. 

During  pregnancy  there  is  a  marked  modification  of 
the  gland.  Freund  observed  augmentation  of  volume  in 
forty-five  out  of  fifty  women.  Lange  established  that  the 
enlargement  commenced  about  the  fourth  month  in  pri- 
miparas  and  the  fifth  month  in  multiparas.      The  gland 


PHYSIOLOGY. 


43 


commences  to  diminish  seven  or  eight  days  after  confine- 
ment and  quickly  recedes  to  normal ;  sometimes  the  hyper- 
trophy continues  through  lactation.  Lange  found  that  out 
of  133  cases  25  did  not  show  any  hypertrophy ;  examina- 
tion showed  that  20  of  these  presented  albuminuria,  and  he 
argued  that  the  relative  insufficiency  of  the  thyroid  has  an 
influence  on  the  kidney.  Experimentation  confirmed  his 
theory.      Lange  removed  four-fifths  of  the  thyroids  in  a 


Fig.  14. — Control  animal,      (v.  Eiselsberg.) 

number  of  cats,  producing  no  symptoms  except  in  those 
with  young,  the  latter  dying  and  the  autopsy  showing  fatty 
degeneration  of  the  kidney.  Several  of  the  operated  cats 
were  impregnated,  developing  albuminuria  and  the  kidney 
degeneration.  This  experiment  shows  a  possibility  of 
eclampsia  being  connected  with  hypothyroidea. 

The  thyroid  has  also  some  effect  upon  the  production 
of  milk.  M.  Wauters  experimented  upon  a  cow  who,  for 
fifteen  days,  had  averaged  11.5  litres  of  milk  per  day. 
He  gave  6  grms.  of  fresh  thyroid  for  ten  days,  during 


44  THE    THYROID    AND    PARATHYROID    GLANDS. 

which  time  the  average  amount  of  milk  rose  to  12.55  litres. 
On  the  following  eight  days  he  gave  8  grms.  thyroid  and 
the  milk  rose  to  13.8  litres  per  diem.  The  average  quan- 
tity of  milk  during  the  twenty  days  the  animal  was  under 
treatment  was  13.17  litres,  being  an  increase  of  1.67  litres 
per  day. 

Lange  took  nine  hens  eighteen  months  old  and  gave  one 
of  them  from  10  to  30  grms.  of  thyroid  daily.  During 
the  following  twenty-eight  days  the  eight  hens  laid  forty- 
two  eggs,  or  an  average  of  5.25  eggs,  while  the  hen  receiv- 
ing thyroid  laid  during  the  same  period  sixteen  eggs ;  the 


Fig.  15. — Aorta   of  thyroidectomized   sheep   showing   atheroma. 
(v.  Eiselsberg. ) 

weight  of  the  eggs  also  increased  10  grms.  Lange  had 
previously  observed  that  a  thyroidectomized  hen  laid  an 
egg  with  a  very  thin  shell  weighing  only  5  grms. 

Metabolism  experiments  have  been  made  during  the 
administration  of  fresh  thyroid  gland,  thyroid  sicca  and 
thyroidin  on  healthy  subjects,  in  myxedema,  in  Basedow's 
disease,  in  obesity  and  in  thyroidectomized  animals,  which 
give  practically  the  same  results.  In  thyroidectomized 
animals  without  thyroid  feeding  there  is  a  greatly  in- 
creased elimination  of  nitrogen  and  a  decreased  elimina- 
tion of  phosphorus,  the  latter  rising  on  the  administration 
of  thyroid.  Boos  kept  a  dog  under  observation  for  two 
months,  estimating  the  elimination  of  nitrogen,  sodium 
chlorid  and  phosphoric  acid.      He  then  administered  3.0 


PHYSIOLOGY.  45 

grins,  and  later  6.0  grins,  thyroid  sicca  daily.  There  was 
an  increased  elimination  if  nitrogen,  sodium  chlorid  and 
phosphoric  acid.  He  then  removed  the  thyroids  and  con- 
tinued the  administration  of  the  thyroid  sicca,  the  nitrogen 
and  sodium  chlorid  elimination  was  further  increased,  but 
the  phosphoric  acid  was  diminished.  The  nitrogen  elim- 
ination in  the  unoperated  animal  rose  from  3.04  to  3.8  and 
from  3.4  to  4.15  and  in  the  operated  animal  from  3.61  to 
5.35.  Magnus  Levy  found  that  the  amount  of  oxygen 
utilized  by  a  subject  at  rest  was  3.1  to  5.36  ccm.,  while  in 
the  obese  it  was  only  2.82  (v.  Noorden  found  2.64).  By 
the  administration  of  thyroid  he  could  raise  the  0  used 
from  2.26  to  2.36  on  the  fifteenth  day  and  to  2.55  on  the 
nineteenth  day,  the  loss  of  weight  in  the  nineteen  days 
being  4  kg.  Theile  and  Nehrung  raised  the  0  from  2.87 
to  3.43,  or  20  per  cent;  v.  Noorden  raised  the  0  used  21 
per  cent,  which  lasted  fourteen  days  after  the  thyroid 
feeding  was  suspended.  Magnus  Levy  treated  a  myx- 
edematous patient  with  thyroid  tablets,  thyroantitoxin  and 
iodothyrin.  With  the  tablets  the  patient  lost  weight  from 
42  to  39.2  kg.,  the  pulse  rose  from  60  to  120,  temperature 
from  36.2  to  37.5,  the  O  used  from  1.22  to  2.15,  the  respira- 
tion quotient  sank  from  0.85  to  0.71.  With  Fraenkel's 
antitoxin  the  amount  of  O  used  was  not  increased  nor  did 
the  pulse  rate  increase,  the  body  weight  did  not  fall  but 
increased  1  kg.  The  iodothyrin  produced  about  the  same 
effect  as  the  tablets,  the  O  rose  from  1.3  to  1.98,  the  respi- 
ration quotient  fell  from  0.83  to  0.74,  the  pulse  rate  rose 
from  60  to  100,  the  body  weight  fell  from  44.2  to  41.9  kg. 
Strive  found  the  O  used  increased  in  a  healthy  subject  by 
the  administration  of  thyroid  tablets  20  to  23  per  cent, 
while  the  increase  of  C02  eliminated  was  somewhat  less. 
Voit  arrived  at  the  same  conclusions. 

Venehren  experimented  with  three  normal  young  men, 
giving  0.1  to  0.3  iodothyrin  per  diem  and  found  no  change 


4(3  THE    THYROID    AND    PARATHYROID    GLANDS. 

in  the  nitrogen  elimination,  but  in  two  older  subjects  there 
was  a  marked  increase.     Dennig  found  that  the  nitrogen 
elimination  was  increased  on  the  administration  of  thyroid 
sicca.     Blubtreu  and  "Wendelstaat,  in  a  metabolism  experi- 
ment on  the  latter,  found  that  by  taking  three  to  four 
tablets,  equal  to  about  2  grains  thyroid  sicca  each,  he  lost 
3  kg.  in  weight  and  15.97  nitrogen,  equal  to  500  grins, 
muscle  substance,  therefore  16  per  cent  of  the  loss  of 
weight  was  due  to  loss  of  muscle  substance.     Scholz  found 
that  by  taking  three  tablets  daily  his  case  lost  no  weight. 
Before  taking  the  tablets  the  elimination  showed  a  nitro- 
gen retention  -4-  3.7567,  while  taking  the  tablets  the  nitro- 
gen retention  was  reduced  to  +  2.6399.     Eichter  found  in 
the  period  before  administration  of  the  thyroid  an  N  re- 
tention +  4.95,  during  the  experimental  period   -(-3.22, 
and  during  the  after  period  +4.0.      Gluzinski  and  Lem- 
berger  obtained  about  the  same  results  by  the  administra- 
tion of  tablets,  but  on  giving  the  fresh  gland  the  retention 
N  of  +2.1  was  reduced  to  — 1.48,  showing  that  while  the 
subject  lost  1  kg.  weight  he  lost  6.24  grms.  N,  equal  to  200 
grms.  muscle  substance,  or  20  per  cent  of  the  total  loss 
was,  therefore,  muscle  substance.      Eichter,  in  order  to 
see  if  it  were  possible  to  reduce  the  weight  without  loss 
of  nitrogen,  put  a  subject  on  a  diet  containing  20.07  N 
and  equal  to  2988  calories,  or  40  calories  per  kg.  of  body 
weight.     He  gave  ten,  fifteen  and  twenty  thyroid  tablets 
two  days  each.     The  subject  lost  2  kg.  in  five  days  with 
a  nitrogen  retention  of  +  12.89,  showing  that  under  suffi- 
ciently nitrogenous  diet  it  is  possible  to  reduce  weight 
without  loss  of  muscle  substance.     In  this  case  the  only 
change  noted  in  the  urine  was  an  increase  of  xanthin 
elimination. 

Schorndorff,  in  a  most  elaborate  and  carefully  con- 
ducted metabolism  experiment  on  a  dog  25  kg.  weight  in 
nitrogen  equilibrium,  found  that  on  the  administration  of 


PHYSIOLOGY.  47 

thyroid  the  elimination  of  nitrogen  was  increased  during 
the  first  eight  days  by  1.59  grms.  per  diem.  The  elimina- 
tion then  sank  to  equilibrium,  then  rose  to  slight  minus 
and  then  again  fell  to  equilibrium.  The  total  nitrogen 
taken  was  729.13,  eliminated  731.96  equal  to  a  loss  of  0.1 
grin,  per  diem.  He  next  increased  the  amount  of  thyroid 
in  order  to  see  if  after  the  elimination  of  the  fat  the  in- 
creased oxidation  would  cause  increased  loss  of  nitrogen. 
During  twenty-two  days  the  animal  received  729.93  N  and 
lost  760.51  N  equal  to  927.0  grms,  muscle  substance;  the 
dog  had  lost  in  all  2200  grms.  weight,  and  had,  therefore, 
lost  1273.0  grms.  fat;  this  loss  was  equal  to  40.0  grms. 
muscle  substance  and  55.0  grms.  fat  daily.  Contrary  to 
other  observers  he  found  that  as  soon  as  the  thyroid  feed- 
ing ceased  the  excessive  nitrogen  elimination  ceased,  the 
animal  gaining  weight  rapidly.  He  concluded  that  the 
increased  elimination  of  nitrogen  in  the  first  few  days  of 
thyroid  feeding  is  due  to  the  elimination  of  extractive  sub- 
stances, while  the  fat  metabolism  really  spares  the  proteid 
nitrogen.  When  the  body  fat  has  been  reduced  to  a  cer- 
tain point  the  nitrogen  elimination  is  increased  by  the 
oxidation  of  proteid. 

The  effect  of  thyroid  feeding  upon  the  metabolism  is 
the  result  of  increased  oxidation  and  consequent  loss  of 
weight.  The  intake  of  oxygen  is  increased,  the  carbon 
dioxid  given  off  is  increased,  the  nitrogen  elimination  is 
increased.  In  the  first  few  days,  probably  by  the  elimina- 
tion of  extractives,  it  is  possible,  by  proper  diet,  to  prevent 
any  loss  of  nitrogen,  the  loss  of  weight  being  then  due  to 
the  oxidation  of  the  fat  and  loss  of  water.  The  chlorid  and 
phosphoric  acid  elimination  are  also  increased,  uric  acid 
elimination  is  not  affected,  but  a  slight  increase  in  the 
xanthin  bodies  has  been  observed,  the  total  quantity  of 
urine  is  usually  increased.  There  is  also  quite  a  percep- 
tible increase  of  perspiration  which,  if  very  marked,  may 
cause  the  urine  to  decrease  in  quantity. 


48  THE    THYEOID    AND    PAEATHYEOID    GLANDS. 

The  administration  of  thyroid  in  large  doses  produces 
a  condition  known  as  thyroidismus,  resembling  in  many 
points  the  symptoms  of  Basedow's  disease.  Exophthal- 
mos has  been  observed  by  Notthaft  in  the  case  of  a  patient 
who  took  very  large  doses  for  obesity.  The  resemblance 
to  Basedow's  disease  was  so  marked  that  the  diagnosis  of 
Basedow's  disease  was  made  before  the  real  cause  was 
discovered.  The  tremors,  mental  depression,  rapid  pulse, 
diagnostic  of  Basedow's  disease,  are  almost  invariably 
produced  by  overdoses  of  thyroid.  Ewald  gives  a  de- 
tailed account  of  the  symptoms  observed  in  various  cases. 
The  pulse  rate  is  increased  to  100-120  or  higher,  palpita- 
tion of  the  heart,  stenocardiac  attacks,  rise  in  temperature, 
a  feeling  of  weakness  with  constriction  of  the  chest, 
tremors,  insomnia,  increased  diuresis  but,  if  the  sweating 
is  very  profuse,  the  twenty-four  hours'  urine  may  be  re- 
duced to  300  ccm.  or  less,  with  increased  elimination  of 
nitrogen,  chlorids  and  phosphoric  acid,  and  may  con- 
tain albumin ;  the  respiration  is  accelerated,  headache  and 
rheumatoid  pains  occur,  eructations,  loss  of  weight  and 
complete  anorexia,  thirst,  dizziness,  loss  of  consciousness, 
increased  flow  of  saliva,  pruritis,  urticaria,  erythema,  ec- 
zema; the  heart  may  become  so  weak  and  the  vessels  so 
dilated  that  the  patient  will  keep  his  head  below  the  level 
of  the  heart.  Sugar  has  been  observed  in  the  urine  by 
Dale,  Jones,  Ewald,  Bennig  and  others.  It  occurred  in 
one  case  at  Mount  Hope.  Levulose  and  inosite  have  both 
been  recorded  as  occurring.  The  mental  symptoms  are 
usually  those  of  depression.  The  writer  took  24  grs.  per 
diem  for  three  days  for  experimental  purposes,  and  the 
depression  was  so  great  that  the  experiment  could  not  be 
continued.  In  other  cases  there  is  a  precordial  anxiety 
with  an  ill-defined  but  very  real  fear  of  impending  danger. 
Maniacal  symptoms  occur,  usually  of  a  melancholic  type, 
and  suicidal  tendencies  may  appear. 


PHYSIOLOGY.  49 

The  action  of  thyroid  feeding  on  the  heart  and  circula- 
tion has  been  studied  by  Oliver,  Schaef  er,  Gley,  Langlois, 
Gurnard  and  Martin.  They  find  that  the  pulse  becomes 
weak  and  rapid.  Oliver,  by  means  of  his  hemodynamo- 
meter  and  arteriometer,  showed  that  the  blood  pressure  is 
very  markedly  reduced,  while  the  arteries  and  arterioles 
are  dilated,  especially  the  peripheral  vessels,  producing 
the  perspiration.  Gurnard  and  Martin  showed  that,  after 
the  vessels  had  been  dilated  and  the  heart  weakened  by 
the  injection  of  thyroid  extract,  they  could  be  rapidly 
restored  to  normal  by  the  injection  of  suprarenal  extract. 

The  blood  changes  after  thyroidectomy  are  more  constant 
than  any  other  pathological  findings  and  offer  an  explana- 
tion to  most  of  the  symptoms  produced  by  the  operation. 
Horsley,  Herzen  and  Eojwitsh  found  that  the  blood  be- 
came more  venous,  the  former  showing  that  the  arterial 
blood  might  contain  less  oxygen  than  was  normal  in  venous 
blood.  Alberti  and  Tizzoni  found  that  the  0  in  the  ar- 
terial blood  was  reduced  from  7  to  8  vol.  to  8  to  11  vol. ; 
Vassali  propounded  the  theory  that  the  red  corpuscles  lost 
their  power  to  combine  with  oxygen,  and  found  that  when 
he  injected  the  expressed  fluid  from  a  gland  into  the  veins 
of  an  operated  dog,  whose  venous  blood  was  almost  black, 
after  a  few  hours  the  blood  became  normal  in  color. 

As  was  previously  mentioned  it  has  been  observed  that 
operated  animals  react  to  external  temperatures  very 
readily ;  the  formation  of  C02  is  immediately  increased  on 
their  being  brought  into  the  cold,  which  only  takes  place 
after  some  time  in  normal  animals.  This  points  to  a  vaso- 
motor disturbance.  Schaefer  has  shown  that  the  intra- 
venous injection  of  thyroid  extract  reduces  blood  pressure, 
and  Oliver  that  the  calibre  of  the  radial  artery  is  increased 
at  the  same  time.  Lewy  made  a  careful  examination  of 
the  blood  in  operated  animals  and  found  that  the  specific 
gravity  was  always  reduced,  but  that  no  other  very  con- 

4 


50  THE    THYEOID    AND    PAEATHYEOID    GLANDS. 

stant  changes  existed;  further,  that  no  relation  appeared 
to  exist  between  the  severity  of  the  symptoms  and  the 
anemic  changes ;  normally  the  leucocytes  are  present  in 
greater  proportion  in  the  veins  than  in  the  arteries  of  the 
gland,  and  the  proportion  is  greater  than  that  found  in 
the  limbs.  Formanck  and  Haskovic  found  the  number  of 
red  corpuscles  invariably  reduced  and  the  leucocytes  in- 
creased, the  total  solids  and  iron  were  diminished.  Duc- 
ceschi  found  that  in  operated  dogs  before  the  commence- 
ment of  the  convulsion  the  serum  albumin  increases  and 
the  serum  globulin  decreases,  the  total  proteids  vary  from 
the  commencement  of  the  convulsions  to  the  death  of  the 
animal,  the  globulin  continues  to  increase,  and  the  serum 
albumin  and  total  albuminoids  decrease  as  in  starvation. 
Bottazzi  finds  the  same  changes  as  Ducceschi;  also  that 
the  red  corpuscles  part  with  their  hemoglobin  very  readily, 
lose  in  specific  gravity  and  that  there  is  an  increase  in 
fibrin.  Masoin  claims  to  have  found  a  toxin  in  the  blood 
of  operated  animals  as  well  as  in  the  urine;  Zuntz  and 
Geppert  found  acid  substances  in  the  blood;  (Hey  found 
that  the  blood  serum  of  operated  animals  produced  typical 
symptoms  when  injected  into  the  blood  of  normal  animals ; 
Edmunds  and  Baldi  on  the  contrary  could  obtain  no  symp- 
toms under  the  same  conditions. 

Excess  of  mucin  has  been  found  in  the  blood  of  myxe- 
dematous patients  and  in  that  of  operated  animals.  Halle- 
burton  analyzed  the  blood  tissues  and  organs  of  a  case  of 
myxedema;  the  tissues  were  finely  minced,  weighed  and 
usually  kept  a  day  in  methyl  alcohol,  decanted  and  the 
tissues  treated  with  lime  water  or  dilute  barium  hydrate 
solution,  allowed  to  macerate  for  a  few  days,  strained,  and 
the  mucin  precipitated  from  the  filtrate  by  the  addition 
of  weak  acetic  acid,  filtered  through  a  weighed  filter, 
washed  with  alcohol  and  ether,  dried  at  100  degrees  C. 
to  a  constant  weight  and  weighed. 


PHYSIOLOGY.  51 

By  this  method  a  number  of  analyses  have  been  made 
with  varying  results. 

The  skin  of  the  thigh  of  a  still-born  child  contained 
0.96  per  cent  mucin ;  the  abdominal  skin  of  children  from 
seven  weeks  to  nine  years  of  age  0.39  to  1.02  per  cent, 
with  an  average  0.766  per  cent;  skin  from  the  same  part 
in  grown  people  contained  0.11  to  0.64  per  cent,  with  an 
average  of  0.385  per  cent;  in  connective  tissue  0.5  per 
cent;  in  Achilles  tendons  0.298  to  0.77  per  cent;  in  the 
parotid  gland  only  a  trace.  In  a  patient  who  had  suffered 
for  ten  years  from  myxedema  Cranston  Charles  found 
fifty  times  more  mucin  than  normal  in  the  skin  of  the 
foot.  Halleburton  found  0.81  to  0.72  per  cent,  and  once 
0.012  per  cent,  average  0.374  per  cent;  the  quantity  in 
the  tendons  was  increased,  1.42  per  cent  in  the  heart,  1.65 
per  cent  in  the  spleen,  2.21  per  cent  in  the  lungs,  0.7  per 
cent  in  the  parotid.  In  the  blood  which  clotted  imper- 
fectly there  was  no  mucin  found,  neither  in  the  peri- 
cordial,  peritoneal  or  cerebro-spinal  fluids.  Horsley  and 
Halliburton  (Brit.  Med.  Jour.,  1885)  found  that  in 
monkeys,  after  the  extirpation  of  the  gland,  mucin  was 
increased  in  the  tissue  as  shown  by  the  following  table : 

Sub- 
Skin.     Tendons.  Muscle.   Parotid,  maxillary.  Blood. 

Normal    0.089 

7th  day  after  operation  .  .   0.045 
29th         "  "  ..   0.108 

49th         "  "  .  .   0.23 

55th         "  "  ..   0.312 

It  was  also  noted  that  the  blood  coagulated  very  slowly, 
but  that  the  proportions  of  serum  globulin  to  serum  albu- 
min were  normal.  It  was  further  observed  that  pigs  did 
not  become  myxedematous  on  thyroidectomy  and  that 
there  is  a  quantity  of  mucin  in  normal  pigs'  tissue,  the 
skin  contained  0.209  per  cent,  tendons  0.403  per  cent, 
muscle  none,  parotid  trace,  submaxillary  gland  0.416  per 


0.009 

0 

0 

0 

0 

0.09 

0 

trace 

0.016 

trace 

0.15 

0 

0.208 

1.036 

trace 

0.24 

trace 

0.17 

0.33 

0.08 

0.255 

trace 

0.072 

0.6 

0.35 

52  THE    THYROID    AND    PARATHYROID    GLAXD3. 

cent,  blood  none,  pancreas  0.009.  In  sheep,  on  whom  the 
operation  had  no  apparent  effect  until  they  were  turned 
out  in  the  cold,  the  "urine  became  thick  with  mucus  when 
the  symptoms  appeared.  Byrom  Bramwell  has  observed 
this  symptom  in  patients  suffering  from  myxedema. 
Halliburton  concludes  from  the  above  analyses  that  the 
percentage  of  mucin  in  the  tendons  of  myxedematous 
patients  slightly  exceeds  normal,  but  that  excess  of  mucin 
in  the  tissues  is  not  pathognomic  of  the  disease.  He  re- 
ports one  case  in  which  the  mucin  was  very  excessive. 
Wagner  claimed  that  by  the  injection  of  mucin  into  the 
vessels  of  cats  he  produced  tremors  and  tetanoid  spasms 
resembling  those  of  thyroidectomy. 

The  pathological  findings  in  thyroidectomized  animals 
are  not  marked  nor  constant,  and  seem  to  be  the  result  of 
starvation  rather  than  toxemia.  In  the  nervous  system 
various  writers  have  found  a  number  of  lesions  but  none 
occur  with  sufficient  regularity  or  uniformity  to  permit 
them  to  be  considered  as  pathognomic  of  the  condition. 
In  the  central  nervous  system  anemia  and  edema  of  the 
brain  and  hyperemia  with  extravasations  in  the  spinal 
cord  have  been  frequently  observed.  Pisenti  found  cavi- 
ties in  the  lumbar  and  costal  portions  of  the  cord  contain- 
ing only  traces  of  nerve  substance,  but  such  cavities  are 
often  found  in  hyperemic  conditions  of  the  brain  and  cord. 
In  the  brain  substance  a  condition  of  encephalitis  paren- 
chymatosis,  accompanied  by  swelling  of  the  nerve  cells 
and  axis-cylinder;  also  a  small  round  cell  in  filtration  of 
the  meninges  of  the  upper  portion  of  the  cord  have  been 
noted  by  Horsley  and  Arthoud.  Mayon  found  a  neur- 
itis vagi.  Langhans  and  Kopp,  examining  the  peripheral 
nerves  in  the  acute  cachexia  of  dogs  and  in  the  more 
chronic  cases  of  monkeys,  men  and  cretins,  found  changes 
of  an  inflammatory  nature.  Although  no  definite  constant 
change  has  been  observed  in  the  nervous  system  there  can 


PHYSIOLOGY. 


53 


be  no  doubt  that  the  symptoms  are  of  central  origin. 
Setoff  has  shown  that  the  tetanic  convulsions  ceased  on 
section  of  the  nerve  trunks ;  Lang  cut  the  sciatic  nerve  in 
an  operated  dog  and  saw  the  twitching  cease  in  the  muscles 
supplied  by  the  nerve ;  Horsley  and  Lang  cut  the  cord  at 
the  eighth  vertebra  and  saw  the  twitching  almost  cease  in 
the  extremities.  The  motor  area  of  one  hemisphere  was 
removed  by  Horsley  in  five  operated  dogs,  the  twitchings 
were  more  marked  on  the  side  which  was  intact.  The  re- 
sults of  these  experiments  prove  that  the  disturbances  are 
of  central  and  not  peripheral  origin. 

Zesas  and  Crede  and  also  Lemke  found  that  the  spleen 
became  enlarged  after  removal  of  the  thyroid,  and  Lohlein 
that  after  the  removal  of  the  spleen  the  thyroid  en- 
larged. Zanda  claimed  that  if  the  spleen  was  removed 
four  weeks  the  thyroid  could  be  removed  without  causing 
any  symptoms,  and  argued  that  the  spleen  produced  toxic 
substances  which  it  was  the  function  of  the  thyroid  to 
neutralize.  Fano  on  repeating  Zanda 's  experiments  did 
not  confirm  his  results.  Hofmeister,  Albertoni,  Tizzoni, 
Gley  and  de  Quervain  failed  to  confirm  Zesas  and  Crede 's 
observations,  and  found  in  five  cases  of  men  dying  of 
cachexia  strumipriva  that  the  spleen  was  unusually  small 
in  four  cases  and  of  normal  size  in  one.  Lang  in  over 
forty  experiments  failed  to  show  any  connection  between 
the  spleen  and  the  thyroid. 

Gley  found  that  by  extirpating  portions  of  the  thyroid 
at  different  times  in  rabbits  he  could  produce  hypertrophy 
of  the  hypophysis  cerebri,  the  weight  of  the  latter  being 
increased  from  0.02,  the  average  normal  weight,  to  0.101 
grms.  There  has  been  much  speculation  as  to  the  possi- 
bility of  the  vicarious  action  of  the  hypophysis  for  the 
thyroid,  which  was  rendered  probable  by  the  former  oc- 
casionally containing  iodin,  but  there  has  been  very  little 
evidence  forthcoming  in  support  of  the  theory. 


54  THE    THYROID    AND    PARATHYROID    GLANDS. 

In  operated  animals  the  temperature  is  usually  normal 
except  during  the  tetanic  spasms,  when  it  may  rise  2  to  5 
degrees  C,  Herzen  on  one  occasion  observing  a  tempera- 
ture of  43.4  degrees  C,  later  the  temperature  falling  be- 
low normal ;  it  may  go  as  low  as  33  degrees  C.  There  is 
marked  susceptibility  to  cold  in  operated  animals,  which  is 
also  very  evident  in  myxedematous  patients.  Munk,  Lang 
and  Kocher  observed  that  the  patients  suffering  from 
cachexia  strurnipriva  were  more  comfortable  in  warm 
rooms,  complaining  of  cold  at  ordinary  temperature.  By 
increasing  the  external  temperature  operated  animals  can 
be  kept  alive  much  longer  and  the  cachexia  and  tetany 
reduced  to  a  minimum.  Whether  the  feeling  of  cold  is 
central  in  origin  or  the  result  of  trophic  changes  of  the 
skin  has  not  been  decided. 

During  the  convulsions  the  respiration  is  increased, 
between  the  attacks  it  is  normal  or  reduced;  the  type  is 
normal.      The  heart's  action  is  increased  in  volume. 

The  urine  shows  no  very  marked  change,  it  is  usually 
decreased  in  quantity,  of  an  increased  specific  gravity  and 
may  contain  albumin  during  the  convulsions.  The  tox- 
icity has  been  found  to  be  increased  by  Gley  and  Laulanie, 
who  claim  that  on  the  injection  of  the  urine  of  an  oper- 
ated animal  into  the  veins  of  an  unoperated  animal  typical 
symptoms  were  produced.  Alonzo  and  others  have  failed 
to  corroborate  their  results  and  could  find  no  appreciable 
difference.  The  nitrogen  and  chlorid  elimination  is  in- 
creased, while  the  phosphoric  acid  is  decreased,  the  pro- 
portion of  neutral  sulphur  to  total  sulphur  is  also  in- 
creased. The  increased  elimination  of  nitrogen  and 
chlorids  is  no  doubt  due  to  the  progressive  anemia  and 
consequent  starvation,  while  the  decreased  phosphoric  acid 
and  increased  neutral  sulphur  may  be  due  to  decreased 
oxidation.  There  is  probably  some  connection  between 
the  phosphorous  metabolism  and  the  thyroid  secretion,  as; 


PHYSIOLOGY.  55 

the  effect  of  congenital  absence  or  early  removal  of  the 
gland  produces  an  arrest  of  development,  especially  of 
the  skeleton,  the  long  bones  and  vertebras  suffering  the 
most.  Hofmeister  made  exact  comparative  measurements 
in  animals  and  found  that  the  growth  of  the  long  bones 
was  decreased  one-third. 

The  influence  of  food  on  the  symptoms  of  thyroidectomy 
is  marked.  Briesacher  found  that  dogs  suffered  less  and 
could  be  kept  alive  longer  if  fed  on  well-cooked  meat  and 
milk,  while  if  given  raw  meat  or  meat  extract  they  suc- 
cumbed much  earlier.  On  milk  diet  the  animals  lived 
longer  or  survived  in  apparently  perfect  health  with  only 
one-third  to  one-fifth  of  the  gland  remaining.  Herbivora 
seem  also  to  suffer  less  than  the  carnivora,  due  presumably 
to  their  vegetable  diet. 


CHAPTER    IV. 

CHEMISTRY    OF    THE    THYROID    GLAND. 

Since  the  thyroid  has  been  proved  to  be  a  secreting 
organ  and  of  vital  importance  to  the  system,  the  chemical 
nature  of  its  secretion  has  been  the  subject  of  most  careful 
research  by  numbers  of  physiological  chemists,  both  in 
Germany  and  England,  their  efforts  having  been  directed 
to  the  isolation  of  the  active  principle.  That  the  gland 
contained  considerable  quantities  of  extractives,  viz :  xan- 
thin,  kypoxanthin,  kreatin,  kreatinin,  paralactic  acid,  ino- 
site  (?),  indicating  high  metabolic  activity  was  early 
proved,  but  none  of  these  could  be  looked  upon  as  the 
active  principle.  White  and  Davis,  working  on  the  hy- 
pothesis that  the  active  principle  was  a  ferment,  obtained 
a  body  which  had  some  activity.  Gourlay  failed  to  find  a 
ferment  which  would  dissolve  mucin,  which  was  consid- 
ered at  that  time  to  be  the  function  of  the  gland,  but  he 
isolated  a  nucleo albumin  which  produced  intravascular 
clotting,  and  which  he  claimed  existed  in  the  colloid  sub- 
stance. Bubnow  extracted  three  different  forms  of  pro- 
teid,  one  apparently  a  globulin;  Notkin  following  on  the 
same  lines  isolated  a  substance  which  he  believed  was  the 
toxic  product  of  metabolism,  which  underwent  decompo- 
sition in  the  gland  through  the  action  of  an  hypothetical 
enzyme.  In  1895  Sigmund  Fraenkel  isolated  a  crystal- 
line alkaloid-like  body  resembling  guanidin  to  which  he 
gave  the  empirical  formula  C6HnN305.  Drechsel  later 
described  a  body  identical  with  that  of  Fraenkel  and 
another  similar  to  it.  Fraenkel 's  thyroantitoxin  was  a 
hygroscopic  crystalline  substance,  soluble  in  water  and 
alcohol,  neutral  to  slight  alkalinity  and  gave  the  alkaloid 

56 


CHEMISTRY    OF    THYROID    GLAND.  57 

reactions.  Injected  into  animals  it  failed  to  produce  a  fall 
in  blood  pressure  but  increased  the  pulse  rate;  admin- 
istered to  thyroidectomized  animals  it  caused  some  im- 
provement in  their  condition.  Fraenkel's  observations 
have  not,  however,  been  confirmed ;  the  epoch-making  dis- 
covery of  Professor  Baumann  of  Freiburg,  in  1896,  of  a 
body  containing  iodin  in  organic  combination  in  the  thy- 
roid of  man  and  of  many  animals,  possessing  the  physio- 
logical characteristics  of  the  gland,  prevented  any  further 
experiments  in  that  line.  Baumann  describes  the  sub- 
stance he  isolated,  which  he  named  ' '  thyroidin, ' '  as  a 
brownish  amorphous  compound  which  decomposed  on 
heating,  giving  off  the  odor  of  pyridin,  it  is  insoluble  in 
water,  sparingly  soluble  in  alcohol  but  dissolves  readily 
in  dilute  alkalis,  being  precipitated  by  acids,  it  gave  no 
proteid  reactions,  and  constantly  contained  phosphorus; 
he  obtained  9.3  per  cent  iodin  in  crystalline  form  from 
this  substance.  Baumann  was  unable  to  complete  his 
work,  owing  to  his  lamented  death  in  1897,  when  physi- 
ological chemistry  lost  one  of  its  ablest  disciples.  His 
method  for  the  isolation  of  the  thyroidin  consisted  in 
digesting  the  gland  for  several  hours  with  a  10  per  cent 
mineral  acid  on  a  sandbath  with  a  return  condenser  and 
extracting  the  residue  with  90  per  cent  alcohol.  He 
proved  that  the  substance  was  iodin  in  proteid  combina- 
tion, and  he  named  it  thyroid  albumin.  Drechsel  and 
Baumann  found  that  the  iodin-containing  proteid  could 
be  dissolved  in  normal  salt  solution,  which  solution  he 
diluted  with  fifteen  volumes  of  distilled  water,  passed 
carbon  dioxid  througli  it,  obtaining  a  precipitate  of  a 
globulin  containing  iodin,  he  added  acetic  acid  to  the 
filtrate  and  boiled,  securing  a  precipitate  of  albumin  which 
also  contained  iodin,  and  therefore  concluded  that  there 
were  two  iodin-containing  proteids  in  the  gland,  a  globulin 
and  an  albumin. 


58  THE    THYROID    AXD    PARATHYROID    GLAXDS. 

Oswald  extracted  99.5  grms.  of  liurnan  thyroid  which 
contained  21.92  nig.  iodin  ten  times  with  normal  salt  solu- 
tion, and  obtained  17.26  mg.  I  in  solution,  being  78.7  per 
cent  of  the  total  I;  Lambach  obtained  97.8  per  cent  in 
solution ;  in  neither  case  was  there  any  iodin  in  inorganic 
combination. 

Oswald  then  proceeded  by  Pick's  method  to  separate 
the  albumins  and  found  that  the  precipitation  commenced 
at  0.26  and  continued  up  to  0.44  saturation,  so  that  at  0.5 
saturation  one  proteid  was  completely  precipitated,  in  the 
nitrate  precipitation  begun  at  0.64  and  continued  up  to 
0.82  saturation  when  the  nitrate  contained  no  proteid. 
He  found  that  the  first  precipitate  contained  iodin  but  no 
phosphorus,  while  the  second  precipitate  contained  no 
iodin  but  contained  phosphorus,  proving  that  the  sepa- 
ration of  the  proteids  was  complete.  The  first  precipitate 
was  dissolved  in  water,  filtered  and  again  half  saturated 
with  ammonium  sulphate.  This  precipitate  was  dialyzed 
till  free  from  ammonium  sulphate,  redissolved  in  alcohol 
(95  per  cent),  filtered  and  the  precipitate  dried.  An 
easier  method  which  dispenses  with  the  tedious  dialyzing 
is  to  dissolve  the  precipitate  from  the  half-saturated  am- 
monium sulphate  solution  in  water  and  precipitate  with 
dilute  acetic  acid,  filter,  dissolve  the  precipitate  in  0.1  per 
cent  sodium  hydrate,  precipitate  with  acetic  acid,  washing 
the  precipitate  with  water  acidulated  with  acetic  acid. 

The  precipitate  is  only  very  slightly  soluble  in  water, 
but  is  more  easily  dissolved  by  the  addition  of  neutral 
salts,  is  very  soluble  in  dilute  alkalis,  is  precipitated  by 
slight  acidulation  with  acetic  or  hydrochloric  acids.  Sat- 
uration with  sodium  chlorid  produces  only  a  slight  cloudi- 
ness, saturation  with  magnesium  sulphate  and  half  satura- 
tion with  ammonium  sulphate  give  complete  precipitation. 
These  reactions  are  those  of  the  globulins  and  Oswald 
designates  the  iodin-containing  globulin  as  thyroglobulin. 


CHEMISTKY    OF    THYEOID    GLAND.  59 

Myosin  is  precipitated  from  its  solution  in  neutral  salts 
by  acids  and  gives  the  other  globulin  reactions,  egg  and 
serum  globulin  are  not  thus  precipitated.  This  substance 
is  not  pseudoniucin,  as  is  often  stated,  as  pseudomucin  is 
not  precipitated  by  acids. 

Thyroglobulin  is  precipitated  by  sulphuric  acid  but  is 
not  soluble  in  excess.  It  is  also  precipitated  by  phos- 
photungstic  acid,  phosphomolybdic  acid,  ferrocyanid  of 
potassium,  acetic  acid,  iodomercuric  potash,  trichloracetic 
acid  and  by  copper  sulphate.  It  gives  the  color  reactions 
for  proteids,  the  biuret  reaction,  Millon  's  reaction,  Adam- 
kiewicz's  reaction,  Mollisch  reaction  and  the  xanthopro- 
teic reaction. 

The  salt  free  solution  becomes  cloudy  on  heating  but 
does  not  coagulate,  on  the  addition  of  10  per  cent  magne- 
sium sulphate  it  coagulates  at  65  degrees  C;  it  contains 
sulphur  which  combines  with  lead.  From  the  strong 
result  of  Mollisch's  reaction  it  may  be  assumed  that  it 
contains  a  large  carbohydrate  group  in  the  molecule; 
after  boiling  for  two  hours  with  5  per  cent  solution  of 
hydrochloric  acid  the  solution  gives  the  red  reaction  with 
a-naphthol  and  sulphuric  acid,  and  also  reduces  Fehling's 
solution  and  ammonia  silver  oxid,  while  it  fails  to  give  the 
typical  phloroglucin  and  hydrochloric  acid  reaction,  it 
gives  a  brown  color  with  this  test,  showing  that  pentose  is 
not  present ;  it  forms  osazone  with  a  melting  point  of  100 
degrees  C.  with  phenylhydrazin  (Hutchinson  failed  to 
obtain  a  reducing  substance  from  sheeps'  thyroid  and 
Eeinbach  from  the  colloid  of  calves '  thyroids) .  In  making 
the  elementary  analysis  of  his  thyroglobulin  Oswald  used 
the  Fresenius  method  for  estimating  the  iodin,  having 
found  that  the  estimation  as  silver  iodid  gave  too  high 
results,  owing  to  the  precipitation  of  silver  chlorid.  As 
the  estimation  of  the  iodin  in  the  preparations  on  the 
market  is  of  value  as  an  indication  of  their  activitv  the 


60  THE    THYEOID    AXD    PAEATHYROID    GLANDS. 

method  is  here  given:  A  weighed  quantity  of  the  sub- 
stance to  be  tested  is  placed  in  a  nickel  or  porcelain 
crucible  with  a  little  water  and  pure  sodium  hydrate, 
evaporated  to  dryness,  a  little  potassium  nitrate  added, 
then  incinerated,  the  residue  dissolved  in  hot  water,  fil- 
tered, and  the  filtrate  placed  in  a  well-stoppered  bottle 
with  about  10  ccm.  of  carbon  disulphid,  acidulated  with 
sulphuric  acid  and  nitrous  acid,  the  solution  is  extracted 
several  times  with  carbon  disulphid,  the  iodin  is  dissolved 
in  the  carbon  disulphid  which  is  washed  two  or  three  times 
with  water.  The  titration  is  then  carried  out  with  a  solu- 
tion of  hyposulphite  .of  soda  standardized  against  a  solu- 
tion of  potassium  iodid  of  known  strength. 

T\ Tien  thyrogiobulin  is  submitted  to  pepsin  digestion  for 
four  weeks  a  gray  brown  flocculent  precipitate  remains, 
which  contains  iodin,  gives  the  xanthoproteic  reaction  but 
neither  the  biuret,  Millon's  nor  Mollisch's  reactions,  and 
is  precipitated  from  its  solution  with  phosphotungstic 
acid.  Hutchinson,  by  digesting  thyrogiobulin  prepared 
by  his  method,  obtained  a  substance  which  gave  no  biuret 
reaction  but  contained  0.8  per  cent  phosphorus,  showing 
that  the  residue  contained  nucleoalbumin  as  well  as  thyro- 
iodin.  Oswald  separated  the  albumoses  and  peptones  in 
the  solution  from  the  pepsin  digestion  by  the  Pick  method 
and  found  that  the  protalbumose  and  deuteroalbumose 
contained  iodin  in  quantity  and  that  the  peptone  B  con- 
tained a  small  quantity,  while  the  heteroalbumose  and 
peptone  A  contained  only  faint  traces,  which  were  prob- 
ably due  to  impurities. 

The  digestion  of  thyrogiobulin  with  trypsin  for  four 
weeks  resulted  in  a  clear  solution,  which  only  gave  faint 
cloudiness  with  ammonium  sulphate,  acetic  acid  produced 
no  precipitate,  showing  that  the  iodin  thyrogiobulin  was 
completely  broken  up,  though  the  solution  contained  iodin 
in  organic  combination.     On  concentration  of  the  solution 


CHEMISTRY    OF    THYEOID    GLAND.  61 

tyrosin  crystals  were  found  and  on  further  concentration 
leucin.  This  decomposition  by  trypsin  digestion  and  the 
iodin  remaining  in  organic  combination  shows  that  the 
iodin  is  not  combined  in  the  tyrosin  group  of  the  thyro- 
globulin  molecule. 

Thyroglobulin  treated  with  10  per  cent  sulphuric  acid 
on  the  sandbath  with  a  return  condenser  is  split  up, 
leaving  a  brown  flocculent  residue  and  a  brown  colored 
solution,  on  filtering  and  washing  till  the  wash  water  is 
free  from  sulphuric  acid,  extracting  with  boiling  alcohol 
till  the  latter  is  no  longer  discolored,  the  alcohol  solution 
evaporated  to  dryness  and  dried  to  a  constant  weight 
leaves  a  brownish  powder,  which  is  insoluble  in  water  or 
acids  but  is  easily  soluble  in  alkali.  It  gives  neither  the 
biuret,  Millon's  or  Mollisch's  reactions  but  gives  the  xan- 
thoproteic reaction,  contains  much  iodin  and  corresponds 
with  Baumann's  thyroidin.  Thyroglobulin  is  split  up 
with  concentrated  acids  and  with  barium  hydrate. 

Oswald  proved  the  physiological  effect  of  the  thyro- 
globulin on  the  metabolism  of  animals,  finding  that  it  in- 
creased the  elimination  of  nitrogen. 

The  second  proteid  separated  from  the  normal  salt  solu- 
tion of  the  gland,  and  which  contained  no  iodin,  contained 
0.16  per  cent  phosphorus,  coagulated  in  a  10  per  cent 
solution  of  magnesium  sulphate  at  73  degrees  C.  with 
<a-naphthol  and  sulphuric  acid  it  gave  a  red  color,  with 
phloroglucin  and  hydrochloric  acid  a  brown  color,  show- 
ing that,  the  carbohydrate  group  is  not  probably  a  pentose ; 
it  also  contained  xanthin  bases  and  is,  therefore,  a  nucleo- 
proteid;  further,  on  being  given  to  animals  it  failed  to 
increase  the  elimination  of  nitrogen. 

Oswald  made  an  elementary  analysis  of  the  thyro- 
globulin from  the  glands  of  man,  pigs,  sheep,  oxen  and 
calves : 


62  THE    THYROID    AND    PAEATHYEOID    GLANDS. 

Calves       Calves 
Man.  Swine.  Sheep.  Oxen.       Goitrous.    Normal. 

Carbon 51.85  52.21  52.32  52.45         52.28 

Hydrogen 6.88  6.83           7.02  6.93            7.04 

Nitrogen    15.49  16.59  15.9  15.92         15.99 

lodin    0.34  0.46           0.39  0.86                           0.56 

Sulphur    1.87  1.86            1.95  1.83           2.00 

Oxygen    (23.57)  (22.15)  (22.42)  (22.01)  (21.61) 


Baldoni  analyzed  the  thyroids  of  calves,  sheep,  pigs, 
)rses 
Rome 


horses  and  oxen  obtained  from  the  slaughter  houses  in 


I  in  dry  I  in 

Albumin.  Globulin.    Nucleoproteid.        Gland.        Globulin. 

Calf   70.5S  61.41  4.15  0.842  1.33 

Sheep 63.16  53.58  3.69  0.652  1.16 

Horse 70.6  58.56  4.45  0.677  1.1 

Ox    68.17  58.49  3.43  0.615  1.01 

Pig    64.21  50.46  3.55  0.311  0.58 

These  analyses  show  that  the  constituents  of  the  thyro- 
globulin  in  all  the  animals  examined  are  almost  propor- 
tionately the  same,  while  the  iodin  may  vary  from  0.0  to 
0.86,  as  in  calves.  The  calves'  glands  which  contained  no 
I  were  from  Zurich  and  were  very  large,  being  from  60  to 
300  grms.  in  weight;  they  were  not  colloid  goitres  but 
hypertrophied  glands  in  which  no  colloid  could  be  seen. 
The  glands  containing  0.36  iodin  were  from  Paris,  their 
average  weight  being  from  15  to  20  grms.,  showing  a  con- 
siderable amount  of  colloid.  These  analyses  of  calves' 
glands  are  of  special  interest,  as  they  show  that  the  goi- 
trous glands  contain  a  thyroglobulin  which  has  the  same 
elementary  analysis  as  in  oxen  but  contains  no  iodin. 
The  thyroglobulin  containing  no  iodin  was  proved  to  be 
physiologically  inert  by  Lyon  and  Oswald,  which  shows 
that  the  physiological  activity  of  the  thyroglobulin  de- 
pends on  its  containing  iodin  in  the  molecule. 

Oswald  made  the  following  analyses  of  the  thyroglobu- 
lin of  human  glands: 


CHEMISTEY    OF    THYROID    GLAND.  63 


O  e> 


Sis'* 


From  Colloid  Goitres  g 

from  Kl  '5-2  I   .      S'S.lo 

*'*  M  *-!  *J       6U§ 

e  w  "j  bo  S  "S  ~        e  -  -2 .~ 

■?  ■eg  "§  S  is  S  ggsSsp 

§  s  e^  .«<=.        s^  s^     p-M-S 

i;  N  ©                  a  <s                  <;          «, 

Carbon    52.02  51.77  51.82  51.85 

Hydrogen    6.91  6.71  7.05  6.88 

Nitrogen   15.32  15.09  15.46  15.49 

Iodin   0.07  0.19  0.07           0.19  0.18           0.34         0.51 

Sulphur    1.93  1.93  1.83  1.87 

Oxygen    23.75  24.31  23.65  23.57 

These  analyses  show  that  the  elementary  composition 
of  the  thyroglobulin  is  the  same  in  men  and  in  animals, 
with  the  exception  of  the  iodin,  and  that  the  latter  is  vari- 
able both  in  animals  and  in  men.  They  further  show  that 
the  thyroglobulin  in  goitrous  glands  is  less  than  in  the 
normal  gland ;  that  the  glands  rich  in  colloid  contain  about 
twice  as  much  iodin  as  normal  glands;  that  the  relative 
iodin  of  the  thyroglobulin  of  the  glands  rich  in  colloid  and 
in  colloid  goitres  is. smaller  while  the  absolute  iodin  con- 
tents of  the  whole  gland  is  higher.  The  fact  that  in  the 
thyroglobulin  from  a  case  of  Basedow 's  disease  where  the 
gland  was  extirpated  during  life,  the  percentage  of  iodin 
is  the  same  as  in  the  colloid  goitres  from  Basel  is  of  par- 
ticular interest ;  also  that  the  gland  of  the  patient  to  whom 
potassium  iodid  had  been  administered,  which  was  an 
enlarged  gland  rich  in  colloid,  contained  a  much  greater 
quantity  of  iodin  than  the  other  Zurich  glands  and  much 
more  than  the  normal  glands  from  Hamburg,  which  seems 
to  prove  that  the  thyroglobulin  of  the  gland  is  capable  of 
combining  with  the  iodin  administered  by  the  mouth  and 
suggests  the  possibility  that  the  symptoms  of  iodism  and 
of  poisoning  with  iodoform  may  be  the  result  of  an  in- 
creased formation  and  consequent  absorption  of  thyro- 
globulin containing  iodin.  Another  point  of  importance 
suggests  itself  from  the  analyses  that  there  is  in  some 


64 


THE    THYBOID    AND    PARATHYROID    GLANDS. 


glands,  if  not  in  all,  a  quantity  of  thyroglobulin  containing 
no  iodin,  which  argues  in  favor  of  the  theory  that  the  thy- 
roglobulin is  secreted  iodin  free,  and  that  the  iodin  enters 
into  combination  with  the  previously  formed  thyroglobu- 
lin. Again,  has  the  thyroglobulin  any  physiological  func- 
tion when  not  combined  with  iodin? 

The  question  arises,  Does  the  thyroid  contain  iodin  thy- 
roglobulin only  when  colloid  is  present  or  at  least  visible 
under  the  microscope,  and  if  not  visible  under  the  micro- 
scope is  iodin  absent  from  the  gland?  If  iodin  is  absent 
from  a  gland  in  which  no  colloid  can  be  found  it  follows 
that  the  thyroglobulin  must  be  first  excreted  from  the  cells 
before  it  combines  with  the  iodin  and  becomes  active. 
The  results  of  a  number  of  analyses  have  apparently 
proved  that  the  amount  of  iodin  bears  a  direct  relation  to 
the  amount  of  colloid  substance.  In  a  gland  which  con- 
tained but  little  colloid  the  analysis  showed  that  the  rela- 
tion of  iodin  thyroglobulin  to  the  total  weight  of  the  gland 
was  1  to  10,  while  in  another,  which  was  full  of  colloid, 
the  relation  was  2  to  3;  this  also  proves  that  by  far  the 
greatest  proportion  of  the  colloid  substance  is  thyroglobu- 
lin; in  fact  so  small  is  the  proportion  of  nucleoproteid 
that  it  is  possibly  only  the  product  of  the  nuclei  of  the 
cells  which  rupture  into  the  follicles  of  the  gland. 

The  amount  of  the  total  iodin  in  the  glands  varies  within 
wide  limits.  Roos  analyzed  many  glands  and  found  that, 
generally  speaking,  the  glands  of  the  true  carnivora  very 
seldom  contain  iodin,  graminivorous  animals  always  con- 
tain it,  rodents  usually  have  it,  also  omnivorous  animals, 
cats  have  very  little.  The  quantity  of  iodin  in  the  glands 
of  man  varies  very  much  according  to  locality.  Weis 
found  the  average  of  glands  in  Silesia  averaged  4.04,  in 
Breslau  3.8  mg.  Oswald  found  that  glands  from  Geneva 
averaged  9.32  mg. ;  Lausanne  7.07  mg. ;  Basel,  6.48  mg. ; 
Zurich,  10.27  mg. ;  Bern,  13.04  mg.     Baumann  found  that 


CHEMISTEY    OF    THYEOID    GLAND. 


65 


in  Freiburg  they  averaged  2.5  mg. ;  Hamburg,  3.8  nag.; 
Berlin,  6.6  mg.  Rosetzki  found  in  Styria  an  average  of 
3.21  mg. ;  Iolen  in  Sweden  3.08  mg.;  Wells  in  Chicago 
10.79  mg.  During  fetal  life  and  early  childhood  iodin  is 
absent  or  only  present  in  traces.  Wells  found  in  Chicago 
as  much  as  0.076  mg.  in  a  child  four  weeks  old,  0.532  mg. 
at  four  years  old  and  3.19  at  seven  years  of  age.  Wells, 
in  a  number  of  analyses  from  Chicago,  tabulates  the 
following : 

Weight  of         Iodin  Per        Total  Iodin 
Sex.  Age.  Cause  of  Death.  Gland.        Gram  in  Mg.         in  Mg. 

Female.  ..  .term  0.135  trace  trace* 

Male term  0.465  trace  trace* 

Female term  0.73  trace  trace* 

Male 4  weeks  Lobular   pneumonia  0.68  0.11  0.076 

Male 4  weeks  Meningitis  0.18  0.42  0.076 

Male 4  years  Diphtheria  0.58  0.92  0.532 

Female 7       "  Phthisis  1.61  1.98  3.19 

Male 45       "  Chronic  nephritis  2.6  2.86                 7.47 

Male 60       "  Brain  tumor  4.39  2.64  11.75 

Male 60       "  Tubercular  peritonitis      2.59  1.67  4.33 

Male 35       "  Pneumonia  3.88  2.58  10.00 

Male 35       "  Peritonitis  3.84  2.66  10.21 

Male 45       "  Pneumonia  10.59  0.99  10.47 

Male 44       "  Pneumonia  6.33  1.52  9.62 

Male 28       "  Endocarditis  3.71  2.74  10.17 

Weight  of     Iodin  Per    Total  Iodin 
Sex.  Age.  Cause  of  Death.  Gland.     Gram  in  Mg.      in  Mg. 

Male 26  years  Liver  abscess  4.47  2.58  11.53 

Male 46  "  Chronic  nephritis  5.16  1.82  9.41 

Male 30  "  Appendicitis  5.79  1.98  11.46 

Male 28  "  Pulmonary  tuberculosis  4.88  2.28  11.15 

Male 49  "  Carcinoma  of  stomach  3.77  1.98  7.46 

Male 30  "  Multiple  Endotheliomata  9.68  1.82  17.62 

Male 35  "  Acute  nephritis  6.66  1.52  10.12 

Male 41  "  Chronic  nephritis  6.53  1.98  12.83 

Female... 25  "  Syphilitic  myelitis  5.44  1.82  9.9 

Male 26  "  Pneumonia  9.01  1.98  17-84 

Male..    ..66  "  Meningitis  5.24  1.52  7.96 

Male 65  "  Pneumonia  4.10  1.22  5.0 

He  also  gives  the  following  from  Boston  and  New  York : 

*  Not  over  0.03  mgrs. 
5 


66  THE    THYROID    AND    PARATHYROID    GLANDS. 


Weight  of 

Iodin  Per 

Total  Iodin 

Sex. 

Age. 

Cause  of  Death. 

Gland. 

Gram  in  Mg. 

in  Mg. 

Male.  .  .  , 

30  years 

Phosphorous  poisoning 

5.48 

2.36 

12.93 

Male 

45       " 

Suffocation 

3.65 

4.94 

18.03 

Female . 

..40       " 

Pneumonia 

4.43 

1.9 

8.42 

Female. 

..25       " 

Appendicitis 

3.84 

2.58 

9.13 

Male.  . 

55       " 

Pneumonia 

4.77 

1.9 

9.06 

Female . 

..40       " 

Pneumonia 

3.54 

4.56 

16.14 

Female . 

..60       " 

Chronic  nephritis 

3.81 

2.13 

8.12 

Male 

60       " 

Pneumonia 

3.47 

1.44 

6.86 

Female . 

..35       " 

Mitral  stenosis 

6.37 

2.20 

14.01 

Male 

47       " 

Poisoning 

3.44 

2.51 

8.63 

Male 

25       '• 

Pneumonia 

4.65 

2.74 

12.74 

Male 

55       " 

Meningitis 

6.18 

2.66 

16.44 

Comparing  his  analyses  with  those  of  Baumann  and 
others  he  concludes  that  the  amount  of  iodin  is  inversely 
proportioned  to  the  amount  of  goitre  in  the  district;  and 
that  the  usually  accepted  theory  that  the  iodin  is  de- 
creased in  chronic  diseases  is  not  according  to  the  results 
of  his  analyses,  but  that  in  old  age  the  amount  of  iodin  is 
much  below  the  average. 

F.  Blum  claims  that  iodothyrin  has  an  inconstant  quan- 
tity of  sulphur  in  the  molecule  and  that  the  molecule  is 
not  saturated  with  iodin.  He  considers  iodothyrin  to  be 
an  unsaturated  iodin  toxalbumin,  that  the  toxin  is  the  iodo- 
thyrin without  the  iodin  and  that  it  renders  harmless  sub- 
stances which  are  being  continually  formed  in  the  organ- 
ism by  means  of  the  iodin.  In  support  of  this  view  Boos 
shows  that  the  saturation  of  the  iodothyrin  molecule  with 
iodin  renders  it  inert,  and  he  finds  that  the  artificially 
produced  iodoalbumins  give  the  same  reactions  as  the 
thyroid  albumins,  and  will  also  produce  iodin  compounds 
similar  to  but  not  identical  with  iodothyrin,  which  he 
claims  proves  that  iodothyrin  is  a  decomposition  product 
from  a  thyroid  iodoalbumin ;  he  also  states  that  after  the 
administration  of  iodid  other  organs  besides  the  thyroid 
form  iodoalbumins,  but  the  thyroid  the  most  readily.  He 
concludes  that  the  hypothetical  metabolic  poison  combines 


CHEMISTEY    OF    THYEOID    GLAND.  67 

with  the  secretions  of  the  thyroid,  the  most  active  of  which 
is  the  one  containing  iodin,  and  that  the  toxin  plus  the 
iodoalbumin  is  the  toxalbumin  of  the  thyroid. 

Fraenkel  extracted  the  dried  gland  with  acetic  acid 
when  the  proteids  were  precipitated  and  found  the  pre- 
cipitate inactive,  while  the  filtrate  was  active  in  obesity. 
He  concentrated  the  filtrate,  treated  with  alcohol  and 
precipitated  with  ether  or  acetone,  obtaining  a  crystalline 
alkaloid  which  increased  the  pulse  rate  when  injected  into 
the  veins  of  a  morphinized  dog  from  56  to  140,  and  de- 
creased the  convulsions  but  did  not  save  the  life  of  thy- 
roidectomized  cats. 

Lanz  states  that  thyroid  sicca  from  swine,  sheep  or 
calves  were  equally  as  good,  and  that  10.0  grms.  of  fresh 
gland  per  day  was  sufficient  to  keep  a  thyroidectomized 
dog  alive.  Wormser  was  unable  to  keep  operated  dogs 
alive  with  any  preparation  except  thyroid  sicca.  Bau- 
mann  and  Goldman  were  able  to  reduce  the  tetanic  attacks 
in  operated  animals  with  from  2  to  6  grms.  thyroidin  per 
diem  and  brought  the  tetanic  convulsions  to  an  end  with 
65.0  grms.,  but  had  to  repeat  the  dose.  Wormser  found 
that  the  precipitate  from  normal  salt  solution  with  acetic 
acid  did  not  prevent  attacks  or  death  in  operated  animals ; 
that  the  proteids  with  dissolved  thyroidin  were  inactive; 
that  synthetically  prepared  iodin  containing  proteids  were 
inactive. 

Hutchinson  published  his  work  on  the  chemistry  of  the 
thyroid  in  1896  and  arrived  at  nearly  the  same  conclusions 
as  Oswald.  His  method  was  to  treat  the  fresh  gland  with 
a  one-tenth  per  cent  solution  of  sodium  hydrate  and  to 
precipitate  with  acetic  acid. 

E.  Lepinois  examined  the  thyroid  for  oxidase  and  found 
an  indirect  oxidase  which  gave  the  blue  reaction  with 
tincture  guaiacum  upon  the  addition  of  hydrogen  dioxid. 
The  presence  of  this  indirect  oxidase  in  the  thyroid  is  of 


68  THE    THYEOID    AND    PAEATHYKOID    GLANDS. 

great  importance,  as  it  may  account  for  the  increased 
oxidation  in  the  system  from  the  administration  of  the 
gland. 

Grautier  claims  to  have  found  arsenic  in  the  glands  of 
dogs,  swine,  sheep  and  man.  The  question  as  to  whether 
this  is  ingested  with  the  food  and  is  merely  as  it  were  an 
impurity  or  whether  arsenic  is  necessary  for  the  normal 
functionation  of  the  gland  has  not  been  decided.  Stein 
has  found  that  many  of  the  garden  vegetables,  such  as 
cabbage,  potatoes,  turnips,  contain  arsenic. 

Paderi  and  Baldi  have  both  found  traces  of  bromin  in 
the  glands  of  dogs.  If  this  should  be  confirmed  and  it 
should  also  be  proved  that  bromin  was  necessary  for  the 
systemic  metabolism,  every  member  of  the  halogen  group 
will  have  been  shown  to  be  a  normal  constituent  of  the 
body. 

Conrad  and  Marchetti  performed  complete  thyroparo- 
thyroidectomy  on  dogs  and  fed  them  with  dibromostearic 
acid.  In  some  cases  it  was  administered  before  the  opera- 
tion, in  one  it  was  continued  after  the  operation,  and  in 
another  the  feeding  was  entirely  postoperative  when  the 
symptoms  were  at  their  height.  This  treatment  appar- 
ently caused  the  attenuation  and  final  disappearance  of  the 
symptoms  for  a  more  or  less  prolonged  period.  Not  only 
was  this  true  of  the  nervous  and  muscular  excitation  and 
depression  but  also  of  the  cachexia,  the  animals  living  in 
a  condition  of  apparent  health.  These  dogs  having  under- 
gone the  same  operation,  were  fed  with  chloriodostearic 
acid  and  two  with  di-iodostearic  acid.  In  the  former 
the  results  were  preeminently  satisfactory,  in  the  latter 
hypodermic  administration  only  gave  good  results.  The 
authors  believe  that  the  salutary  influence  of  the  halogens 
studied  upon  operated  animals  are  to  be  attributed  to  the 
effect  of  the  bromin  and  iodin,  and  to  a  more  complex 
physiological  action  representing  within  certain  limits 
the  functions  of  the  thyroparathyroid  tissues. 


CHEMISTRY    OF    THYROID    GLAND.  69 

There  seems  to  be  no  doubt  that  in  Oswald's  iodin  con- 
taining thyroglobulin  we  have  at  least  the  chief,  if  not  the 
only,  active  principle  of  the  gland,  and  it  is  certain  that 
iodin  in  the  molecule  is  also  necessary  for  perfect  func- 
tionation.  That  thyroglobulin  without  iodin  in  the  mole- 
cule is  physiological  is  probable,  but  to  what  extent  is  not 
at  present  known.  The  phosphorus  containing  proteid, 
which  has  been  classed  as  a  nucleoproteid,  though  small 
in  quantity,  may  have  some  physiological  activity,  as  the 
gland  has  some  connection  with  the  phosphorous  metabo- 
lism and  the  calcification  of  the  bones. 

There  are  three  distinct  theories  as  to  the  function  of 
the  thyroid  gland;  that  it  is  a  secreting  organ  which  is 
necessary  for  the  metabolism  or  for  the  nourishment  of 
the  system ;  that  it  secretes  an  antitoxin  for  the  poisonous 
products  of  metabolism ;  that  there  is  a  form  of  digestion 
in  the  gland  whereby  the  toxic  substances  of  metabolism 
are  converted  into  useful  and  necessary  substances  for 
the  organism  by  the  action  of  an  enzyme,  and  that  in  the 
absence  of  these  necessary  substances  the  symptoms  are 
produced. 

The  advocate  of  the  latter  theory  is  Notkin,  who  found 
that  by  the  injection  of  2.0  grms.  per  kg.  of  the  acetic  acid 
precipitate  from  a  normal  salt  solution  extract  of  the  fresh 
gland  into  the  veins  or  abdominal  cavity  of  a  partially 
thyroidectomized  dog  he  produced  death  with  symptoms 
of  general  paralysis,  while  repeated  small  doses  produce 
a  cachexia  resembling  myxedema.  His  theory  is  that 
there  are  two  substances  being  continually  produced  in 
the  body  as  a  result  of  metabolism,  one  a  toxin  which 
produces  tetanic  symptoms  if  allowed  to  accumulate,  the 
other  is  a  peculiar  proteid  substance,  which,  if  similarly 
allowed  to  accumulate,  produces  the  cachectic  condition 
known  as  myxedema.  According  to  this  theory  it  is  the 
function  of  the  thyroid  to  antagonize  these  substances. 


70  THE    THYROID    AND    PARATHYROID    GLANDS. 

The  first  substance  is  destroyed  by  the  action  of  Fraenkel  's 
thyroantitoxin,  which  is  basic  in  nature  and  unites  with 
and  neutralizes  the  toxin,  the  convulsions  in  operated  ani- 
mals are  due  to  an  arrest  in  the  supply  of  the  antitoxin. 
The  second  substance,  which  produces  myxedema,  is  con- 
veyed to  the  thyroid  by  the  blood  and  thus  split  up  by  a 
ferment  into  two  constituents,  one  of  which  is  of  the  nature 
of  a  carbohydrate  and  is  set  free,  the  other  is  a  proteid 
which  unites  with  an  organic  iodin  compound,  rendering 
it  harmless.  He  denies  that  the  iodin  compound  is  able 
to  prevent  the  convulsions  which  follow  thyroidectomy, 
and  he  believes  that  it  can  only  cure  myxedema  when 
there  is  some  thyroid  tissue  left  to  utilize  it,  and  make  it 
unite  with  the  proteid  substance,  which  he  claims  produces 
myxedema.  This  complicated  and  ingenious  theory  has 
several  objections:  one  is  that  it  has  been  shown  that  the 
colloid  substance  without  the  antitoxin  will  prevent  or 
mitigate  the  convulsions ;  that  the  presence  of  an  enzyme 
in  the  thyroid  is  purely  hypothetical,  there  being  no  ex- 
perimental evidence  of  the  existence  of  such  a  substance, 
and  further,  if  this  theory  were  correct  thyroid  feeding 
should  make  myxedematous  patients  worse  instead  of 
which  it  is  curative. 

The  antitoxic  theory  has  been  advocated  by  Ewald, 
Blum  and  others,  being  expressed  in  two  ways,  that  the 
antitoxin  in  the  gland  seizes  on  the  toxin  in  the  blood, 
acting  upon  it  in  the  gland  itself,  and  that  it  is  only  the 
neutralized  toxin  which  passes  into  the  blood  stream,  thus 
acting  in  an  analogous  manner  to  the  bodies  of  Langer- 
hans  in  the  pancreas.  The  other  theory  is  the  result  of 
the  doctrine  of  autointoxication,  so  ably  brought  forward 
by  Albu,  by  which  he  attempts  to  prove  that  almost  all 
diseases  result  from  this  cause;  it  presumes  that  con- 
stantly during  life  the  normal  metabolism  is  producing 
lower  chemical  forms  derived  from  proteid,  which  accu- 


CHEMISTRY    OF    THYEOID    GLAND.  71 

ululating  through  failure  of  excretion  or  neutralization, 
poison  the  system,  producing  various  symptoms.  The 
antitoxin  theory  of  the  function  of  the  gland  presumes 
that  the  active  principle  of  the  gland  neutralizes  or  de- 
composes one  or  more  of  these  toxins  into  innocuous  sub- 
stances. It  is  probable  that  the  decreased  oxidation  re- 
sulting from  thyroid  insufficiency  will  prevent  the  perfect 
metabolism  of  the  body  proteids  and  if  these  imperfectly 
oxidized  substances  are  toxic,  then  by  increasing  the 
oxidation  they  will  be  destroyed  and  in  this  sense  the 
thyroid  may  be  considered  antitoxic  in  its  functions.  So 
far  the  advocates  of  this  theory  have  failed  to  isolate  or 
detect  these  toxins  in  the  blood  or  in  the  urine  of  thyroid- 
ectomized  animals.  As  previously  mentioned  one  or  two 
observers  claim  to  have  produced  typical  symptoms  by 
injecting  the  serum  or  urine  of  operated  dogs  into  healthy 
animals,  but  their  results  have  not  been  confirmed.  Re- 
cently Basedow 's  disease  is  said  to  have  been  successfully 
treated  by  injecting  the  serum  from  a  thyroidectomized 
goat  into  the  patient  but  even  if  this  success  is  confirmed 
it  does  not  prove  the  theory.  In  opposition  to  the  anti- 
toxic theory  are  arrayed  nearly  all  the  facts  of  experi- 
mental and  chemical  physiology,  the  extract  of  the  gland 
reduces  blood  pressure,  increases  the  amount  of  oxygen 
absorbed;  increases  the  elimination  of  carbon  dioxid,  in- 
creases the  nitrogen  elimination  by  the  urine  and  increases 
temperature  in  normal  subjects,  besides  producing  a  va- 
riety of  symptoms  which  are  hardly  compatible  with  the 
theory.  Again,  in  cretinism  and  myxedema,  two  diseases 
which  are  admittedly  due  to  thyroid  insufficiency,  the 
patients  arrive  at  a  certain  stage  and  remain  stationary, 
while  if  the  diseases  were  due  to  the  accumulation  of 
toxins  they  would  be  progressive.  All  the  metabolism 
experiments  show  that  the  action  of  the  gland  substance 
is  in  close  relationship  with  the  general  metabolism  and 


f  I  THE    THYROID    AND    PARATHYEOID    GLANDS. 

it  has  the  direct  effect  of  increasing  the  assimilation  of 
oxygen.  How  important  oxygen  is  to  the  systemic  func- 
tions is  self-evident ;  even  a  small  excess  of  carbon  dioxid 
in  the  atmosphere  of  a  room  will,  by  reducing  the  amount 
of  oxygen  inhaled,  produce  discomfort.  The  proper  dis- 
tribution of  oxygen  to  the  various  organs  and  tissues  is 
the  .sine  qua  non  of  life  and  if  this  supply  is  decreased  the 
cell  nutrition  and  activity  must  be  impaired.  The  special 
connection  of  the  thyroid  with  the  organs  of  generation 
cannot  be  explained  by  the  theory  that  its  function  is 
antitoxic. 

Of  the  function  of  the  parathyroids  little  is  known  at 
present;  they  appear  to  be  connected  with  the  thyroid  and 
perhaps  to  have  some  special  relation  to  the  nervous 
system. 

From  its  origin  and  mode  of  evolution  it  would  seem 
that  the  thyroid  is  to  be  considered  as  associated  with  the 
respiratory  gaseous  exchange  of  the  blood  and  tissues,  the 
phenomena  following  its  destruction  by  disease  or  experi- 
ment are  to  be  interpreted  as  a  disturbance  of  the  gaseous 
metabolism,  especially  with  the  mal assimilation  of  oxygen 
by  the  body  tissues,  to  which  are  probably  correlated  the 
subnormal  temperature,  twitchings,  loss  of  fat,  and  the 
languor  and  weakness  of  brain  and  muscle  tissue  asso- 
ciated with  the  condition.  It  is  also  probable  that  there 
is  some  connection  between  the  thyroid  and  the  phosphor- 
ous metabolism. 


CHAPTER    V. 
GOITRE. 

Goitre,  struma— Goitre,  French;  kropf,  German;  gozzo, 
Italian;  lobanillo,  Spanish;  wen,  Derbyneck,  English. 

The  term  goitre  was  first  used  by  the  early  writers  for 
the  enlargement  of  any  organ  or  gland  which  was  so  evi- 
dent as  to  be  a  visible  deformity,  but  has  in  recent  years 
been  restricted  to  enlargement  of  the  thyroid  gland. 
Struma  is  an  abbreviation  from  struere  and  ruma  defined 
as  struere  rumam  seu  propendentem  de  collo  mammam. 
It  was  also  termed  gutter  turgidum  or  bronchocele. 

It  is  remarkable  that  the  ancient  writers  on  medicine 
have  left  so  few  records  of  so  evident  a  deformity  as 
goitre.  Plinius,  Vituw  and  Ulpian  mention  the  disease, 
looking  upon  it  as  a  divine  punishment.  The  same  view 
seems  to  have  existed  in  the  middle  ages,  as  on  many  of 
the  old  churches  where  goitre  is  endemic  the  griffins  and 
devils  are  represented  with  goitres  as  if  it  were  a  mark  of 
depravity.  Marco  Polo,  writing  in  the  thirteenth  century, 
mentions  its  existence  in  the  highlands  of  Central  Asia. 

Paracelsus,  in  the  fifteenth  century,  describes  the  dis- 
ease as  occurring  in  the  Tyrol,  pointing  out  its  association 
and  probable  connection  with  cretinism.  Malcarne,  of 
Turin,  published  in  1789  a  series  of  scientific  observations 
followed  in  1800  by  Fodere.  From  this  time  the  litera- 
ture has  increased  until  it  has  become  so  voluminous  that 
in  1893  the  catalogue  of  the  Surgeon-General's  Library 
at  Washington  contained  no  less  than  1857  references  to 
articles  on  the  thyroid  gland  and  its  diseases. 

Goitre  occurs  as  an  endemic,  epidemic  and  sporadic 
disease.     The  endemic  form  occurs  in  more  or  less  circum- 


74  THE    THYEOID    AND    PARATHYROID    GLANDS. 

scribed  areas  in  both  hemispheres,  being  always  associated 
with  cretinism.  To  what  extent  the  disease  exists  in 
affected  districts  can  be  gathered  from  the  government 
military  statistics.  In  Switzerland,  between  the  years 
1875  and  1881,  no  less  than  12,277  men  were  rejected  on 
account  of  the  deformity;  in  Italy,  between  1859  and 
1864,  301  out  of  every  10,000  inhabitants  were  rejected, 
of  whom  209  were  cretins  and  92  goitrous;  in  1883,  in 
Piedmont,  there  were  154  cretins  for  every  10,000  inhabit- 
ants; in  Lombardy,  205,  and  in  Venice  23.  The  total 
population  of  these  three  provinces  was  9,565,000,  of 
whom  12,882  were  cretins  and  128,730  goitrous. 

A  remarkable  feature  of  the  disease  is  its  periodicity,  at 
one  time  declining  in  a  particular  neighborhood  and  then 
again  increasing,  or  it  may  suddenly  appear  in  a  district 
where  it  was  previously  unknown.  Denny  states  that 
when  the  French  first  settled  at  Pittsburg  goitre  was 
unknown,  and  that  in  1798  it  had  become  so  prevalent  that 
out  of  1500  inhabitants  150  were  goitrous,  after  1806  it 
began  to  decline. 

There  are  many  cases  on  record  where  an  epidemic  of 
acute  goitre  has  occurred  in  places  where  it  was  previously 
unknown.  In  1877,  in  the  barracks  at  Belfort,  Vigny  and 
Eichard  observed  900  cases  among  5300  men.  In  1889 
Angieras  saw  18  cases  in  a  wing  of  a  pavilion  among  a 
regiment  of  infantry  at  Clermont-Ferrand.  In  Neu-Brei- 
sach  in  the  years  1847,  1858,  1869  and  1870,  an  epidemic 
occurred  in  every  fresh  regiment  that  arrived,  appearing 
as  a  rule  in  summer  or  autumn.  Bottini  observed  an 
epidemic  among  the  prisoners  in  Pallanga.  In  all  cases 
these  epidemics  have  occurred  in  barracks,  prisons  or 
seminaries,  the  inhabitants  of  the  town  not  being  affected. 
In  nearly  all  cases  these  epidemics  occurred  in  districts 
where  goitre  was  endemic  and  among  persons  who  had 
come  from  a  nongoitrous  district,  who  are  liable  to  an 


GOITEE.  75 

acute  attack  which  soon  disappears  after  leaving  the  goi- 
trous district.  It  has  also  been  observed  that  persons 
afflicted  with  goitre  may  partially  or  entirely  lose  their 
goitre  on  removing  to  a  nongoitrous  district.  Horses, 
dogs,  pigs,  goats,  cats  and  sheep  have  been  observed  to 
acquire  goitre  on  being  brought  into  an  affected  district, 
which  gradually  subsides  after  a  week  or  a  month. 

Goitre  is  endemic  in  certain  districts  of  nearly  every 
country  in  the  world,  being  more  especially  pronounced 
in  the  deep  river  cut  valleys  descending  from  high  moun- 
tain ranges  where  the  river  water  has  become  stagnated 
and  formed  marshes.  In  Europe  the  valleys  of  the  Alps, 
the  Pyrenees,  the  Carpathians,  in  the  Black  Forest,  in 
Thiiringen,  in  the  Hartz  mountains,  in  Sussex,  Hampshire 
and  Derbyshire  in  England  it  is  particularly  prevalent. 
The  valleys  of  the  Apennines  are  an  exception,  it  being 
very  rare  in  mid-Italy.  In  Eussia  it  occurs  in  Finland 
and  in  the  Eastern  provinces.  In  Asia  it  is  met  with  in 
the  valleys  of  the  Himalayas,  in  Tibet  and  in  Siberia,  in 
Japan,  Sumatra,  Ceylon  and  Java.  In  Africa,  in  Moroc- 
co, Abyssinia,  in  the  Niger  valley,  in  the  Azores  and  in 
Madagascar.  In  North  America  it  is  found  in  Canada, 
in  the  Hudson  Bay  territory,  in  Connecticut,  Michigan, 
New  Hampshire,  Vermont  and  Mexico.  In  South  Amer- 
ica in  the  valleys  of.  the  Cordilleras,  in  the  central  parts 
of  Brazil  and  in  Chili.  Franklin  observed  it  in  Green- 
land, so  that  no  zone  is  free  from  it.  Altitude  appears 
to  have  little  effect,  it  having  been  observed  in  the  Hima- 
layas 4000  feet  above  sea  level. 

A  disease  which  is  so  universal,  and  which  incapacitates 
so  many  citizens,  besides  being  accompanied  by  cretinism, 
a  still  more  terrible  affliction,  has  naturally  been  the 
subject  of  much  scientific  research.  The  etiology  of  the 
endemic  goitre  and  cretinism  has  exercised  the  minds  of 
pathologists  ever  since  scientific  observations  were  made 


76  THE    THYROID    AND    PARATHYROID    GLANDS. 

upon  disease.  Such  an  evident  and  unsightly  deformity 
and  the  deplorable  and  pitiable  condition  of  the  cretins 
has  caused  an  immense  amount  of  experimentation  and 
theorizing.  St.  Leger  has  collected  no  less  than  forty-two 
different  views  on  the  genesis  of  goitre.  Light,  air,  sea- 
son, temperature,  race,  configuration  of  the  country, 
trauma,  continued  artificial  pressure  on  the  neck  from  the 
carrying  of  loads  on  the  head,  etc.,  have  all  had  their 
advocates,  but  as  yet  no  very  satisfactory  theory  has  been 
brought  forward.  In  the  Alps  the  natives  ascribe  the  dis- 
ease to  the  drinking  of  snow  or  glacier  water  but  as  goitre 
is  endemic  in  countries  where  there  is  no  perpetual  snow 
and  no  glaciers  this  cannot  be  the  primary  cause.  There 
is,  however,  much  evidence  to  show  that  it  is  the  result  of 
drinking  water  which  rises  or  passes  over  certain  geolog- 
ical strata,  viz:  the  marine  sediments  of  the  paleolithic 
trias  and  tertian  formations.  Others  again  claim  it  is  due 
to  a  specific  organism  in  the  waters  of  the  affected  dis- 
tricts. Virchow  is  of  opinion  that  the  drinking  water  is 
the  medium  through  which  the  disease  is  produced  and 
that  the  geological  conditions  in  which  the  water  rises  or 
through  which  it  flows  are  the  primary  cause.  Kocher  is 
of  the  same  opinion.  Lucke  claims  the  disease  to  be  of 
micro-organic  origin,  and  that  the  organism  only  grows  on 
a  specific  medium,  entering  the  body  with  the  drinking- 
water.  The  Sardinian  commission  on  goitre  and  cretin- 
ism concluded  that  no  geological  formations  were  entirely 
free  from  the  disease  but  that  it  was  more  prevalent  on 
the  tertian  than  on  the  more  recent  strata.  Bircher,  after 
the  most  careful  and  painstaking  research,  is  of  opinion 
that  endemic  goitre  is  confined  to  definite  geological  forma- 
tions, viz :  Devonian,  Silurian,  coal  dyas,  trias  and  tertian ; 
that  it  does  not  appear  on  volcanic  or  crystalline  rocks,  on 
the  river  sediments  or  chalk  formations  nor  on  the  qua- 
ternian  or  fresh  water  sediments. 


GOITRE.  77 

Drinking  water  is  considered  by  all  observers  to  be  the 
medium  by  which  the  disease  enters  the  system,  a  very 
important  proof  of  which  is  that  certain  wells  in  the  af- 
fected districts  produce  the  disease  when  their  water  is 
used  for  drinking  purposes ;  so  well  is  this  recognized  by 
the  inhabitants  that  it  is  a  common  practice  for  men  to 
drink  from  these  Kropfbrunnen  so  as  to  acquire  the  de- 
formity, thus  escaping  military  service.  These  wells  have 
been  known  from  the  earliest  times,  Vitravius  writes 
"  Acqueculis  in  Italia  et  Alpibus  nationi  medullorun  est 
genus  aqum  quam  qui  bibent  effecuenter  turgitis  gutturi- 
bus."  It  has  also  been  observed  that  families  or  indi- 
viduals in  affected  districts  who  abstain  from  drinking 
from  the  Kropfbrunnen,  using  cistern  water  instead,  re- 
main free  from  the  disease,  and  even  those  who  have 
already  acquired  the  disease  are  cured  or  relieved  by 
abstaining  from  the  affected  water.  In  some  districts 
goitre  has  entirely  disappeared  on  the  inhabitants  obtain- 
ing a  fresh  water  supply.  An  instructive  example  of  this 
is  the  case  of  Rupperswyl  near  Aarau,  which  changed  its 
water  supply  in  1884,  drawing  it  from  a  goitre-free  dis- 
trict. The  reduction  in  the  affected  children  was  most 
marked.  In  1885  59  per  cent  were  goitrous,  in  1886  44 
per  cent,  in  1889  25  per  cent,  in  1895  11  per  cent.  Against 
the  theory  of  the  origin  of  the  disease  being  in  the  drink- 
ing water  is  the  fact  that  certain  places  drawing  their 
water  from  the  same  source  as  a  goitrous  district  are 
goitre  free,  which  is  possibly  accounted  for  by  the  tribu- 
taries of  the  stream  either  diluting  the  water  on  its  way 
to  the  unaffected  district  or  by  a  tributary  from  an  in- 
fected spring  bringing  the  infection  into  the  stream  be- 
fore its  arrival  at  the  affected  area. 

Many  experiments  have  been  made  to  produce  goitre 
in  animals.  Bircher  gave  five  young  dogs  water  from  a 
Kropfbrunnen  for  a  month,  as  well  as  mixing  the  sediment 


/O  THE    THYROID    AND    PARATHYROID    GLANDS. 

of  the  well  with  their  food  but  none  of  them  developed  the 
disease,  which  he  explains  by  the  short  duration  of  the 
experiment  and  by  the  animals  being  too  young,  goitre  not 
usually  developing  in  the  child  before  the  fifth  year.  Lus- 
tig  and  Carle  experimented  with  a  horse  and  found  that 
by  giving  the  water  from  an  infected  well  one  lobe  stead- 
ily and  progressively  enlarged;  this  they  removed  when 
the  other  lobe  began  to  enlarge,  returning  to  its  normal 
size  on  giving  the  animal  ordinary  water.  Thirteen  dogs 
were  treated  in  the  same  manner,  only  one  developing  an 
enlargement  of  the  left  lobe,  and  on  its  removal  the  right 
lobe  began  to  swell,  but  returned  to  normal  on  filtering  the 
water.  Ten  other  dogs  remained  normal  on  being  fed 
with  boiled  or  filtered  infected  water.  These  experiments 
are  not  conclusive,  the  number  of  animals  developing 
goitre  is  very  small  and  it  has  been  observed  that  animals 
in  goitrous  districts  that  show  enlargement  of  the  gland 
usually  become  normal  in  a  few  weeks  without  change  of 
environment. 

From  the  above  it  seems  most  probable  that  the  water 
which  arises  from  or  passes  over  certain  geological  forma- 
tions contains  a  "something"  which  produces  goitre.  The 
nature  of  this  ' '  something ' '  has  been  investigated  with  the 
following  results: 

Zschokke  observed  that  the  inhabitants  on  the  right  bank 
of  the  Aar  were  more  subject  to  goitre  and  cretinism  than 
those  on  the  left;  only  this  difference  could  be  observed 
that  the  water  on  the  right  bank  was  more  contaminated 
with  animal  and  vegetable  extractions  than  the  left. 
Blondeau  and  Tinot  analyzed  the  inorganic  constituents 
of  infected  wells  for  lime  salts,  carbonates,  phosphates, 
magnesia,  etc.,  but  obtained  no  constant  results.  Chatiu 
in  1852  found  that  the  water  from  the  mountains  and  in 
the  valleys  affected  contained  less  iodin  than  normal, 
which  is  of  interest  in  connection  with  Baumann's  dis- 


GOITEE.  79 

covery  in  1896  that  the  thyroid  contained  iodin.  Later 
investigations  show  so  many  exceptions  that  the  absence 
of  iodin  cannot  be  considered  as  a  cause.  These  analyses 
show  that  the  inorganic  salts  of  the  drinking  water  have 
no  connection  with  the  disease. 

Humboldt  considered  that  goitre  and  cretinism  were  the 
result  of  an  infection.  Vest,  Bramberg,  Schausberger, 
Troxler  and  Hirsch  were  of  the  same  opinion.  Virchow 
believed  that  the  vapor  contained  a  substance  which  acted 
upon  the  organism  as  a  miasma.  Liicke  maintained  that 
the  miasma  of  goitre  was  similar  to  the  marsh  miasma  of 
malaria. 

The  bacteriological  examinations  of  the  waters  of  in- 
fected springs  have  not  yet  produced  any  definite  results. 
Klebs  found  an  infusoria  which  he  named  naviculicula, 
Bircher  a  diatom  eucyonama,  also  a  comma-shaped  bacil- 
lus with  snake-like  movements,  but  all  efforts  to  produce 
the  disease  in  animals  with  cultures  failed.  Tavel  ex- 
mined  clear  water  from  springs  which  produced  the  dis- 
ease and  isolated  thirty-three  different  bacteria,  while  in 
neighboring  wells  he  could  only  find  nine.  Still  none  of 
these  were  apparently  capable  of  producing  the  disease. 
Lustig  and  Carle  examined  twenty-five  wells  in  the  valley 
of  Aosta  by  modern  bacteriological  methods.  They  were 
unable  to  find  the  bacillus  of  Bircher.  They  found,  how- 
ever, a  bacillus  which  was  constant,  liquefying  gelatin, 
but  which  produced  no  effects  when  injected  into  animals 
in  pure  culture. 

The  etiology  of  endemic  goitre  is  still  not  proven,  the 
weight  of  evidence  points  to  the  water  which  springs  from 
or  passes  over  certain  geological  formations  being  the 
means  of  entrance  into  the  system  of  some  contagium 
vivum  which  has  as  yet  escaped  detection. 

Occasionally  in  districts  where  goitre  is  endemic  it  may 
be  congenital.     Demme  records  37  cases  out  of  642  goi- 


80  THE    THYROID    AND    PARATHYROID    GLANDS. 

trous  children  that  he  examined.  When  congenital  it  may 
be  so  large  as  to  interfere  with  delivery,  growing  with  ex- 
treme rapidity,  causing  compression  of  the  trachea,  which 
may  be  fatal.  It  is  usually  hyperplastic,  though  Demme 
has  observed  both  the  cystic  and  mixed  forms.  Its  weight 
at  birth  may  reach  10  to  20  grins.,  the  normal  being  from 
2  to  5  grms.  Virchow  and  Bednar  found  an  enlarged  thy- 
mus present  in  most  cases ;  Eulen- 
berg  and  Libert  found  persistence 
of  the  thymus  in  goitrous  children 
and  in  adults.  The  persistence 
of  the  thymus  has  been  observed 
in  cases  of  Basedow's  disease,  and 
Ohlmacher  finds  it  in  cases  of  so- 
called  idiopathic  epilepsy  with 
lymphatic  constitution. 

Sporadic  goitre  is  a  totally  dif- 
ferent disease  from  the  endemic 
form,  having  no  connection  as  far 
as  is  known  with  any  specific  in- 
fection. It  is  usually  observed  in 
young  chlorotic  girls  who  have 
developed  early,  and  is  probably 
the  result  of  sexual  disturbances, 
often  suppression  or  partial  sup- 
pression of  the  menses,  trauma  or 
hyperemia  of  the  gland.  The  na- 
ture of  the  employment  may  have 
Fig.  16.— Circular  stricture  some  connection  with  the  produc- 

of    the    trachea    from    goitre.    ti(m  q£  sporadic  goitre.     Halm  ob- 
(Demme.)  . 

served  in  Luzerches  that  goitre 
was  a  common  affection  among  the  workers  in  needle  fac- 
tories ;  since  this  form  of  industry  has  ceased  in  the  district 
the  deformity  has  disappeared.    There  is  another  form  of 


GOITEE. 


81 


goitre  which  is  occasionally  observed  in  acute  diseases 
.which  will  be  described  later. 

The  enlargement  of  the  gland  may  be  unilateral,  bilat- 
eral, or  median,  extending  in  various  directions.  In  some 
cases  no  deformity  may  be  visible  and  even  its  detection 
by  palpation  is  attended  with  much  difficulty.  In  the 
median  form  the  swelling 
extends  in  the  direction  of 
the  suprasternal  notch,  en- 
tering the  mediasternal  re- 
gion. In  these  cases  the 
gland  moves  with  the  res- 
piration and  may  entirely 
disappear  on  deep  inspira- 
tion. This  form  is  termed 
by  Fodere  "goitre  ende- 
dans"  or  "goitre  plon- 
geant. ' '  In  other  cases  the 
swelling  may  be  held  fast 
by  the  surrounding  tissues 
under  the  sternoclavicular 
articulation  and  the  first 
rib,  causing  great  pressure 
on  the  gland,  preventing 
diagnosis  by  palpation.  Oc- 
casionally it  descends  into 
the  pleural  cavity  as  far  as 
the  aortic  arch,  pressing  on  the  lung.  It  may  extend  into 
the  submaxillary  region,  making  but  little  visible  deform- 
ity, though  reaching  as  far  as  the  mastoid  process.  This 
is  the  most  common  direction  of  enlargement  in  children 
and  in  congenital  cases.  Another  form  is  known  as  mov- 
able goitre,  "Wandernden  Kropf"  of  Wolfler,  the  result 
of  excessive  mobility  of  the  trachea  and  larynx,  so  that  at 
one  time  it  may  be  behind  the  sternum  and  at  another  in 
6 


Fig.  17. — Bayonet  shaped  tra- 
chea from  bilateral  goitre. 
( Demme. ) 


82 


THE    THYBOID    AND    PARATHYROID    GLANDS. 


its  normal  position,  differing  from  the  "goitre  plongenat" 
in  the  regularity  of  the  latter 's  movements  with  the  res- 
piration. 

Goitres  may  grow  to  a  great  size,  it  being  not  uncom- 
mon to  see  one  the  size  of  a  small  child's  head  hanging 
as  low  as  the  breasts.  When  only  one  lobe  is  enlarged 
it  is  usually  the  right,  the  disease  as  a  rule  commencing 


Fig.   18.  —  Showing  the   enlarged  veins  in  goitre.      (WCilfler. 


in  this  lobe,  a  possible  reason  being  that  the  venous  return 
from  the  right  lobe  is  more  interfered  with  owing  to  the 
relation  of  the  vein  to  the  heart.  As  the  goitre  increases 
in  size  so  does  the  circumference  of  the  neck,  the  sterno- 
hyoid, sternothyroid  and  sternocleidomastoid  muscles  be- 
ing pressed  forward  and  outward,  usually  atrophying,  but 
in  some  instances  they  become  hypertrophied,  producing 


GOITR] 


83 


great  pressure  upon  the  gland  and  through  it  on  the 
trachea,  being  occasionally  the  cause  of  sudden  death. 

In  nearly  all  cases  of  goitre  the  most  pronounced  symp- 
tom is  the  interference  with  the  respiration,  which  may  be 
caused  in  three  ways,  the  prolongation  of  the  trachea  in 
relation  to  the  larynx;  nar- 
rowing of  the  lumen  of  the 
trachea;  changes  in  the 
walls  of  the  trachea;  in 
severe  cases  all  three  may 
occur.  Simple  prolonga- 
tion of  the  trachea  in  rela- 
tion to  the  larynx  is  usually 
not  accompanied  with  se- 
vere symptoms,  but  when 
accompanied  by  distortion 
of  the  trachea  and  conse- 
quent narrowing  of  the  lu- 
men the  respiratory  symp- 
toms are  much  more  severe. 
The  contraction  can  be 
either  unilateral,  bilateral  or  circular,  sometimes  taking 
the  form  of  the  letter  D,  at  others  becoming  half-moon 
shaped.  In  double  seated  compression  the  trachea  as- 
sumes a  bayonet  shape.  Compression  of  the  anterior 
of  the  trachea  is  rare,  being  due  to  enlargement  of  the 
isthmus  of  the  gland.  After  the  compression  has  lasted 
some  time  trophic  changes  in  the  wall  of  the  trachea  take 
place  so  that  the  rings  become  soft,  the  trachea  kinking 
as  it  were,  sometimes  causing  sudden  death. 

At  autopsy  in  these  cases  the  microscopical  examination 
shows  hyperemia  of  the  mucous  membrane,  fatty  degen- 
eration of  the  rings  and  also  of  the  muscles  of  the  posterior 
wall  of  the  trachea.  One  of  the  results  of  the  narrowing 
of  the  trachea  is  an  enlargement  of  the  lower  portion  of 


Fig.  19.— Bending  and  narrowing  of 
the  trachea  by  goitre.      (Demrne.) 


84 


THE    THYKOID    AND    PAEATHYEOID    GLANDS. 


the  tube  followed  by  chronic  bronchitis.     Very  rarely  the 
larynx  is  also  compressed  when  the  same  degenerations 

occur.  Pressure  on  the  esophagus 
and  consequent  narrowing  with  de- 
generation of  the  walls  may  occur, 
causing  difficulty  in  swallowing; 
complete  occlusion  of  the  esopha- 
gus has  been  recorded. 

The  arteries  and  the  veins  of  the 
gland  suffer  from  dilatation,  the 
walls  becoming  thin  and  brittle. 
The  auricles  dilate  and  dilatation 
or  hypertrophy  of  the  heart,  with 
fatty  degeneration  of  the  heart 
muscle,  occur  in  a  large  proportion 
of  cases. 

Of  the  nerves  the  recurrent 
laryngeal,  the  superior  laryngeal, 
the  vagus,  the  sympathetic  and  the 
hypoglossus  are  affected  in  certain 
cases. 

The  degenerations  of  the  gland 
in  goitre  are  of  the  nature  of  an 
hypertrophy  with  hyperplasia  of 
the  glandular  constituents,  the  re- 
sult of  hyperemia.  The  changes 
are  various,  resulting  from  the  increase  of  the  separate 
constituents  of  the  gland,  either  of  the  parenchyma,  the 
colloid  substance  or  of  the  connective  tissue,  which  may 
be  classified  into  four  forms,  but  which  are  rather  a  ques- 
tion of  degree  than  of  definite  pathological  lesions. 

Struma  parenchymatose  seu  follicularis  arises  from  a 
hyperplasia  of  the  follicles,  commencing  by  the  formation 
of  zones  or  grooves  in  the  interstitial  tissue,  containing 
small  empty  follicles,  lined  with  cylindrical  or  cubical 


Fig.  20.— Goitre  of  accessory 
thyroids.      (Adjutolo.) 


GOITRE. 


85 


epithelium,  which  increase  in  size,  forming  perfect  nod- 
ules containing  colloid.      The  septa  of  these  follicles  be- 


Fig.  21. — Retrosternal  goitre  in  a  deep-seated  thyroid  lobe. 
( Wuhrman. ) 

come  thin ;  the  epithelium  disappears,  the  walls  give  way, 
forming  larger   follicles   of  irregular   shape.     Zielinska 


Fig.  22.  —  Intrathoracic  goitre.      (Dittrich.) 

claims  to  have  seen  the  colloid  mass  in  the  veins  and  ar- 
teries at  this  stage.      The  struma  of  the  gland  does  not 


8G 


THE    THYEOID    AND    PARATHYROID    GLANDS. 


differ  from  normal  except  in  the  formation  of  blood  ves- 
sels and  connective  tissue,  the  latter  surrounding  the 
follicles  and  forming  a  nodule  while  the  gland  remains 
soft  to  the  touch,  rarely  reaching  any  great  size.  There 
is  only  a  graduated  difference  between  this  form  and  the 


Fig.  23. — Follicular  goitre,      (v.   Eiselsberg. ) 


struma  gelatinosa  seu  colloides,  the  amount  of  colloid  sub- 
stance being  greater,  owing  to  a  larger  number  of  the 
follicles  and  alveoli  coalescing  from  the  atrophy  and  pres- 
sure from  the  excess  of  colloid  forming  struma  cystica. 
Grutkneckt  differentiates  another  form  of  cyst  formed  by 
the  breaking  down  of  the  walls  of  the  alveoli  by  hyalin 
degeneration.  The  cysts  consist  of  a  capsule  of  fibrous 
connective  tissue  which,  in  the  earlier  stages,  is  lined  with 
epithelium  and  filled  with  an  opaque  fluid  containing  fatty 


GOITEE. 


87 


detritus,  degenerated  red  blood  corpuscles,  leucocytes, 
blood  coloring  matters,  crystals  of  calcium  oxalate,  choles- 
terin,  ammoniomagnesium  phosphate,  sodium  and  potas- 
sium chlorid,  of  a  brown  or  greenish  color,  showing  that 
hemorrhage  has  taken  place.  In  old  cysts  there  is  often 
calcification,  which  prevents  the  walls  from  falling  to- 


Fig.  24.— Goitre  marked  by  diffuse  follicular  hypertrophy. 

gether  when  the  fluid  is  withdrawn,  broken  septa  often 
remain  in  the  cyst,  showing  on  section  an  apparent  net- 
work through  the  mass,  which  may  also  contain  varicose 
veins,  bleeding  easily. 

Struma  Vasculosa.— In  acute  cases  of  hyperemic  goitre 
the  tumor  fluctuates,  pulsates,  is  compressible,  and  a  mur- 
mur is  audible  on  auscultation,  while  the  neighboring  ves- 
sels of  the  neck  are  congested.     In  chronic  cases  there  is 


88 


THE    THYBOID    AND    PAEATHYROID    GLANDS. 


an  equal  dilatation  of  both  arteries  and  veins,  the  latter 
being  varicose. 

Struma  fibrosa  is  produced  by  a  hyperplasia  of  the  in- 
terstitial tissue  and  is  generally  the  result  of  or  contem- 
poraneous with  a  struma  follicularis.  In  the  centre  of  a 
nodule  there  is  a  yellowish  cartilaginous  shining  spot  of 


Fig.  25. — Colloid  goitre,      (v.  Bruns.) 

connective  tissue.  Occasionally  the  connective  tissue  is 
diffuse.  The  nodules  are  scattered  through  the  gland  tis- 
sue in  circumscribed  areas,  it  being  rare  for  the  whole 
gland  to  be  affected.  Each  nodule  appears  like  an  en- 
cysted tumor  with  a  nucleus,  in  which  are  rings  of  con- 
nective tissue,  from  which  strands  pass  toward  the  centre. 
The  intermediate  spaces  usually  contain  follicles.  The 
nodules  are  poorly  supplied  with  vessels,  but  sometimes 


GOITEE. 


89 


are  vascular  and  then  contain  extravasations  of  blood 
pigment,  these  ultimately  becoming  cysts.  According  to 
Gutkneckt  both  the  centre  and  periphery  may  break  down 
and  become  calcined. 

Symptomatology.  — The  symptoms  of  goitre  are  very 
varied  in  intensity,  in  many  cases  a  very  large  goitre  may 


Fig.  26.  — Follicular  goitre  with  ectasia  of  the  veins  of  the  skin. 

cause  little  or  no  inconvenience,  except  for  the  disfigure- 
ment of  the  neck,  while  a  small  retropharyngeal  nodule 
may  produce  the  greatest  irritation.  In  general,  the 
goitre  makes  its  appearance  at  or  shortly  after  puberty, 
though  occasionally  as  late  even  as  the  fortieth  year,  being- 
more  common  in  females  than  in  males  and  may  be  either 
chronic  or  acute.     The  acute  form  is  that  described  above 


90 


THE    THYROID    AKD    PAEATHYEOID    GLAXDS. 


as  hyperemia,  appearing  suddenly  in  a  few  hours  or  days. 
The  tumor  usually  affects  the  whole  gland,  producing 
sometimes  a  loud  circulatory  murmur  and  by  pressure 
dyspnea,  generally  disappearing  in  a  few  days,  sometimes 
returning  to  become  chronic. 


Fig. 


-Cystic  goitre.      (Billroth.) 


The  chronic  form  makes  its  appearance  slowly  without 
attracting  the  attention  of  the  patient  either  in  one  lobe  or 
both,  progressing  slowly  but  surely  to  its  maximum.  At 
first  no  other  symptoms  are  remarked  except  the  deform- 
ity, with  perhaps  passing  flushings  of  the  head  and  face ; 
as  the  gland  increases  in  size  the  symptoms  increase.  In 
cases  of  small  or  medium  sized  goitres  there  is  pressure 
on  the  veins  of  the  neck  in  the  neighborhood  of  the  gland 
and  on  the  lymphatics,  producing  dilatation  of  the  veins, 


GOITEE. 


91 


cyanosis  of  the  face,  particularly  on  straining  or  after  a 
heavy  meal,  headache  and  a  feeling  of  anxiety.  As  the 
turnor  increases  in  size  symptoms  of  pressure  on  the 
trachea  and  paralysis  of  the  glottis  and  vocal  cords  may 
appear,  the  latter  caused  by  the  pressure  on  the  recurrent 
laryngeals.  The  pressure  on  the  veins  is  sometimes  very 
great  and  should  one  of  them  be  opened  it  will  spurt  like 


Fig.  28. — Cystic  goitre,      (v.  Brims.] 


an  artery.  Should  a  tracheotomy  become  necessary  the 
venous  congestion  ceases  as  soon  as  the  breathing  is  re- 
stored. From  the  pressure  of  the  tumor  the  position  of 
the  veins  and  arteries  may  be  altered,  the  jugular  being 
pressed  toward  the  middle  line  of  the  neck  and  the  carotid 
outward  to  a  distance  of  10  to  12  cm.  where  it  may  be  pos- 
sible to  feel  it.  Irregularity,  increased  frequency  and 
palpitation  of  the  heart  are  common  symptoms  in  young 
chlorotic  girls,  probably  due  to  irritation  or  paralysis  of 


92  THE    THYEOID    AND    PARATHYKOID    GLANDS. 

the  vagus.  Of  still  greater  importance  are  respiratory 
disturbances  which  may  come  from  direct  pressure  on  the 
trachea,  from  nerve  irritation  or  paralysis.  The  difficulty 
of  breathing  increases  with  the  growth  of  the  tumor  and 
may  be  greater  at  one  time  than  another.  When  a  tra- 
cheal catarrh  supervenes  or  the  goitre  is  suddenly  in- 
creased by  hyperemia,  which  may  occur  from  the  exercise 
of  running  upstairs  or  walking  uphill,  very  serious  results 
are  produced,  requiring  tracheotomy,  or  even  death  may 
supervene  before  the  operation  can  be  performed.  There 
is  also  a  stridor  on  expiration,  which  can  be  heard  from  a 
distance ;  as  the  pressure  on  the  trachea  increases  so  does 
the  stridor.  In  advanced  cases  there  is  also  a  sound  on 
inspiration ;  patients  at  this  stage  are  compelled  to  inspire 
while  talking  quietly  or  to  use  expiration  to  say  a  word 
quickly,  when  there  follows  a  long,  rough  whistling  in- 
spiration. If  a  laryngeal  or  lung  catarrh  supervene  a 
serious  condition  may  arise  of  dyspnea  or  asphyxia.  The 
"goitre  plongeant, "  or  substernal  tumor  plays  an  impor- 
tant part,  in  some  cases  the  tumor  pressing  the  trachea 
between  the  sternum  and  the  vertebral  column.  This  only 
happens,  however,  when  the  tumor  becomes  fixed  under 
the  sternum.  Pressure  on  the  laryngeal  nerves  produces 
either  an  inflammatory  thickening  of  the  perineurium  or 
an  irritable  condition  of  the  nerve,  still  more  often  a  pres- 
sure atrophy  with  resulting  paralysis  or  paresis  of  the 
vocal  cords.  According  to  Wolfler  this  condition  occurs 
in  10  per  cent  of  the  cases.  This  form  has  been  called 
goitre  asthma,  producing  severe  symptoms  of  suffocation, 
through  the  reduction  of  the  rima  glottidis,  combined  with 
narrowing  of  the  trachea.  Examination  with  the  laryn- 
goscope shows  paralysis  of  the  muscles ;  in  making  a  diag- 
nosis, neurosis,  hysteria,  catarrhal  conditions  of  the  air 
passages,  emphysema  and  congestion  of  the  venous  circu- 
lation must  be  excluded. 


GOITRE. 


Iii  the  submaxillary  form  the  posterior  auricular  nerve 
may  be  affected,  causing  pain  behind  the  ear  and  in  the 
occipital  portion  of  the  occipito-frontalis  muscle.  The 
sympathetic  is  also  subject  to  pressure,  producing  hemi- 
crania  and  other  disturbances ;  probably  the  exophthalmos 
of  Graves '  disease  is  in  part  at  least  produced  by  irritation 
of  the  sympathetic;  occasionally  the  spinal  accessory  is 
affected,  producing  clonic  spasms  of  the  neck.  Pressure 
on  the  esophagus  from  a  retropharyngeal  goitre  may  pro- 
duce dysphasia  to  such  an  extent  as  to  prevent  the  patient 
from  swallowing,  or  a  piece  of  food  may  be  arrested  in 
the  lumen  and  have  to  be  forced  down  with  the  sound. 
Wolfler  found  the  narrowing  of  the  esophagus  in  13  per 
cent  of  his  cases.  There  is  a  change  of  the  physiognomy, 
which  is  of  some  diagnostic  value,  the  head  is  thrown 
back,  the  neck  stretched,  the  mouth  widened  and  drawn 
backward,  giving  the  face  a  stupid  expression.  There  is 
also  an  intellectual  weakness  with  mental  irritability ;  epi- 
leptic spasms  occur,  whether  connected  with  the  disease 
or  merely  a  coincidence  it  is  difficult  to  say. 

Considering  the  number  and  importance  of  the  various 
tissues  in  the  neighborhood  of  the  gland,  whose  functions 
may  be  interfered  with  by  pressure  from  the  tumor,  the 
number  of  symptoms  which  may  be  produced  must  neces- 
sarily be  very  great.  As  the  enlargement  may  take  place 
in  such  a  direction  as  to  become  substernal,  subclavicular, 
submaxillary  or  retropharyngeal  palpation  may  be  diffi- 
cult or  impossible.  Pressure  may  be  exerted  upon  the 
veins  and  lymphatics  of  the  neck  as  well  as  upon  the 
carotid  arteries,  on  the  pneumogastric  nerve  affecting  the 
heart  and  the  digestive  function;  upon  the  recurrent 
laryngeals,  the  superior  laryngeals  and  the  phrenic  affect- 
ing the  respiration;  upon  the  glossopharyngeal,  the  pos- 
terior auricular,  the  spinal  accessory,  the  sympathetic  and 
very  rarely  the  brachial  plexus.      It  may  produce  con- 


94  THE    THYROID    AND    PARATHYROID    GLANDS. 

traction  or  occlusion  of  the  trachea  and  esophagus,  while 
an  excessive  secretion  of  the  colloid  material  will  produce 
the  symptoms  of  thyroidismus,  or,  as  is  more  often  the 
case,  the  gland  becomes  cirrhotic,  when  the  myxedema- 
tous symptoms  of  hypothyroidea  and  athyroidea  will 
occur. 

The  diagnosis  of  goitre  presents  no  difficulties,  provided 
the  enlargement  is  in  such  a  direction  as  to  be  visible  or 
palpable.  The  disease  has  to  be  differentiated  from 
lymphomata  of  the  neck  glands,  lymphosarcoma  and  the 
enlarged  glands  of  Hodgkin's  disease.  The  swollen 
glands  can  be  differentiated  by  the  position  and  shape; 
the  slow  growth,  the  cachexia  and  the  condition  of  the 
blood  help  the  diagnosis.  Should  the  tumor  be  retro- 
pharyngeal the  diagnosis  may  be  impossible.  In  the  ab- 
sence of  the  isthmus  the  tumor  no  longer  follows  the 
movements  of  the  throat.  Wolfler  gives  the  following 
symptoms  in  these  cases :  Suffocation,  especially  at  night, 
pressure  on  the  jugular  by  sinking  the  head,  a  feeling  of 
pressure  in  the  aperture  of  the  thorax,  a  paralysis  of  the 
left  recurrent  laryngeal  nerve,  one  side  exophthalmos, 
fixed  larynx,  narrowed  trachea,  and  in  some  cases  the 
pulse  of  the  carotid  may  be  different  from  the  radial. 

For  the  differentiation  of  the  different  forms  of  goitre 
the  following  points  are  of  service : 

Simple  Hyperemia.— -Is  transient,  usually  connected 
with  menstruation  or  sexual  causes;  the  throat  becomes 
round  and  enlarged,  the  larynx  is  no  longer  prominent, 
the  examiner  feels  only  indistinctly  the  contour  of  the 
gland,  which  is  either  soft  to  the  touch  or  unaltered  in 
consistency. 

Struma  Parenchymatose.—Ts  of  soft  consistency  with 
sharply  defined  borders,  the  size  usually  about  that  of  a 
pigeon's  egg,  or  it  may  increase  to  that  of  a  hen's  egg,  in 
the  latter  case  it  is  visible ;  this  form  is  usually  unilateral. 


GOITRE.  95 

Struma  Vasculosa.— Does  not  reach  any  great  size,  is 
compressible  by  the  finger,  feeling  like  a  sponge,  a  circu- 
lation nrurmur  can  be  heard  on  auscultation. 

Struma  Co lloides.— Produces  equal  enlargement  on  both 
sides,  the  skin  over  the  gland  is  tight,  the  jugular  is  di- 
lated, the  symptoms  are  those  of  hyperthyroidea. 

Struma  Fibrosa.— Contains  hard  nodules  from  the  size 
of  a  pea  to  that  of  a  hen's  egg,  with  the  conglomeration 
of  the  nodules  the  gland  may  grow  to  a  great  size,  the 
separate  nodules  being  distinct  to  the  touch ;  in  calcifica- 
tion the  hardness  is  increased,  the  symptoms  are  those  of 
myxedema. 

Mixed  Goitre.— Is  the  largest  and  is  usually  of  the 
hanging  type,  extending  sometimes  as  low  as  the  breasts. 

For  the  palpation  of  goitre  it  is  best  for  an  assistant  to 
grip  the  back  of  the  neck  from  behind,  so  that  the  gland 
does  not  slip  from  under  the  fingers  of  the  examiner. 
Aspiration  is  occasionally  used  to  determine  the  nature 
of  the  goitre,  but  it  is  not  without  danger. 

The  course  of  uncomplicated  goitre  is  slow,  it  may  be 
from  early  youth  to  old  age,  though  the  patient  usually 
seeks  surgical  aid  either  before  twenty  or  between  twenty 
and  thirty. 

Besides  the  goitre  of  the  true  thyroid  gland  the  acces- 
sory thyroids  may  become  enlarged  either  separately  or 
with  the  mother  gland. 

Accessory  thyroids  are  of  three  kinds :  those  which  are 
not  connected  with  the  mother  gland,  isolated  or  true 
accessory  glands;  those  which  are  connected  to  the  main 
gland  by  a  band  of  connective  tissue,  false  accessory 
glands,  and  those  which  are  connected  by  a  band  of  thy- 
roid tissue,  connected  accessory  glands.  They  can  be 
further  divided  according  to  their  positions  in  relation  to 
the  main  gland— anterior,  posterior,  superior,  inferior  and 
lateral— or  according  to  the  anlage  from  which  they  were 
developed. 


96  THE    THYEOID    AND    PABATHYEOID    GLANDS. 

Accessory  thyroids,  derived  from  the  middle  or  lateral 
aril  ages,  can  be  either  substernal,  endothoracic  or  retro- 
clavicular,  and  are  the  most  common.  Occasionally  the 
isthmus  is  lower  than  normal  and  when  goitrous  it  lies 
under  the  manubrium  sterni.  As  a  rule  the  accessory 
gland  grows  downward  from  the  isthmus  analogous  to  the 
pyramid  which  grows  upward.  This  form,  when  not  con- 
nected with  the  isthmus,  is  sometimes  called  aortic  struma ; 
others  are  connected  with  the  inferior  apex  usually  of  the 
left  lobe  and  are  in  the  thoracic  cavity;  endothoracic 
glands,  reaching  to  the  pericardium  and  usually  lying 
behind  the  trachea;  others  may  pass  behind  the  trachea, 
pressing  upon  the  lungs,  and  are  termed  intrathoracic, 
while  others  may  be  grouped  behind  the  sternum.  The 
posterior  accessory  glands  may  lie  behind  the  larynx  and 
esophagus,  when  a  goitre  will  contract  the  esophagus; 
occasionally  they  occur  within  the  larynx  and  trachea,  and 
even  in  the  substance  of  the  hyoid  bone.  The  diagnosis 
of  goitre  of  the  accessory  glands  is  attended  with  great 
difficulty. 

The  thyroid  gland  is  often  in  an  abnormal  position  and 
may  be  so  low  as  to  lie  completely  behind  the  sternum. 

The  treatment  of  goitre  is  either  prophylactic  or  me- 
dicinal, including  organotherapy  and  surgical. 

The  prophylactic  treatment  consists  in  leaving  a  district 
in  which  goitre  is  endemic,  in  abstaining  from  drinking 
the  water  or  boiling  it  thoroughly  first.  If  there  is  a  dis- 
position to  goitre,  the  patient  should  abstain  from  any  ex- 
ercise which  may  produce  hyperemia  of  the  neck.  Re- 
moval to  the  seacoast  is  often  curative  in  the  early  stages. 

Of  drugs  iodin  has  been  used  for  many  years,  at  first 
empirically,  being  given  as  powdered  sponge,  which  con- 
tains iodin  in  organic  combination  (spongin).  Coindet, 
of  Geneva,  in  1820,  was  the  first  to  recognize  that  the 
iodin  was  the  active  principle,  and  since  his  time  the  iodids 


GOITRE.  97 

have  been  the  orthodox  treatment.  Kocher,  who  has  made 
a  special  study  of  the  disease,  and  has  had  an  exception- 
ally large  experience,  is  of  opinion  that  90  per  cent  of  all 
goitres  can  be  cured  or  improved  by  iodin  treatment,  so 
that  only  10  per  cent  need  come  to  the  operating  table. 

Iodin  can  be  administered  either  by  external  applica- 
tion, by  the  mouth  or  by  injection. 

A  satisfactory  method  of  applying  iodin  externally,  pre- 
venting the  disfigurement  by  staining  the  skin,  is  to  apply 
a  bandage  soaked  in  from  10  to  20  per  cent  solution  of 
potassium  iodin  during  the  night; 

Monal,  Mill  and  Gove  have  used  a  salve  containing 
about  3  per  cent  biniodid  of  mercury  with  good  results, 
even  in  congenital  cases.  Gussenbauer  recommends  iodo- 
form ointment.  The  internal  administration  of  iodin  is 
more  effective  either  in  the  form  of  potassium  or  sodium 
iodid,  Lugol's  solution  or  iodoform,  but  only  in  small 
doses,  care  being  taken  not  to  produce  iodism.  The  treat- 
ment only  gives  satisfactory  results  in  young  rjeople  and 
at  the  commencement  of  the  disease.  The  colloid  and 
fibrous  goitres  are  not  influenced  by  iodin  treatment. 

In  1873  the  English  physician,  Moyen  Indenland,  gave 
the  fresh  thyroid  gland  of  the  sheep  in  some  cases  of  goitre 
with  good  results.  Emminghaus  and  Eeinhold,  having 
observed  the  improvement  in  the  mental  condition  in  cases 
of  cretinism  and  myxedema  by  the  administration  of  thy- 
roid, administered  it  to  some  goitrous  insane  patients. 
The  mental  condition  of  these  patients  was  not  improved 
but  the  goitres  disappeared,  v.  Bruns  administered  thy- 
roid tablets  to  350  goitrous  patients  and  found  8  per  cent 
cured,  marked  improvement  in  36  per  cent,  slight  im- 
provement in  30  per  cent,  no  improvement  in  26  per  cent. 
The  treatment  produced  the  best  results  in  young  patients 
with  follicular  hypertrophy.  In  struma  fibrosa  the  nodes 
were  not  reduced  in  size,  but  the  intermediate  tissue  was 

7 


98  THE    THYROID    AND    PAEATHYEOID    GLANDS. 

absorbed,  reducing  the  size  of  the  goitre,  rendering  opera- 
tion unnecessary. 

v.  Bruns  studied  the  action  of  the  thyroid  treatment  on 
twelve  goitrous  dogs  by  removing  a  portion  of  the  gland 
before  and  after  treatment  and  found  that  the  effect  of  the 
feeding  was  to  increase  the  amount  of  colloid  in  the  tissue 
of  the  struma,  it  being  apparently  greater  than  in  the  nor- 
mal gland,  the  lymphatics  being  gorged  with  colloid,  the 
undeveloped  tissue  was  absorbed,  the  vessels  partially  ob- 
literated. The  total  result  he  described  as  a  trophoneu- 
rotic atrophy  of  the  gland.  Kocher  excised  a  colloid 
goitre  after  several  weeks'  treatment  with  thyroid  and 
found  that  only  a  portion  of  the  alveoli  contained  colloid, 
and  those  that  did  contain  colloid  were  only  from  a  third 
to  a  quarter  full.  He  came  to  the  conclusion  that  there 
was  no  difference  between  the  action  of  the  thyroid  and 
iodin.  Kijewski  saw  symptoms  of  Basedow's  disease  dur- 
ing treatment.  K.  Serapin  found  that  colloid,  cystic  and 
vascular  goitre  were  not  benefited,  but  that  the  fibrous 
goitres  became  somewhat  softer  and  smaller. 

v.  Mikulicz  claims  to  have  good  results  from  the  admin- 
istration of  thymus. 

The  direct  injection  of  tincture  of  iodin  or  iodoformol 
into  the  gland  was  first  introduced  by  Skoldberg  in  1855, 
and  later  by  Luton  in  Rheims  and  Liicke  in  Strassburg. 

Pring  investigated  the  effect  of  the  injection  of  iodin 
into  the  glands  of  animals.  He  found  that  two  or  three 
days  after  the  injection  of  0.2  ccm.  of  tincture  of  iodin 
there  was  a  serofibrous  exudation  at  the  point  of  punc- 
ture with  necrosis  of  the  cells  of  the  parenchyma,  which 
necrosis  did  not  take  place  if  salt  solution  were  used  in- 
stead of  the  iodin.  After  one  or  two  weeks  there  was  a 
formation  of  connective  tissue.  After  the  injection  of 
alcohol  there  were  the  same  results,  but  to  a  less  degree. 
After  the  injection  of  iodoform  there  was  parenchymatous 


GOITKE.  99 

coagulation  necrosis  without  fatty  degeneration  of  the 
cells.  The  colloid  substance  was  not  absorbed  as  a  result 
of  the  injection.  The  injection  is  not  without  danger,  as 
sudden  death  may  occur  if  the  injection  is  made  into  one 
of  the  larger  vessels.  Another  danger  is  that  the  injection 
may  go  into  the  trachea.  The  operation  must  be  per- 
formed under  strict  antiseptic  precautions.  The  danger 
of  injection  into  a  vessel  can  be  guarded  against  by  with- 
drawing the  canula  and  observing  if  it  is  followed  by 
blood;  if  so,  another  place  must  be  chosen  for  injection. 
To  be  sure  that  the  needle  is  in  the  goitre  it  is  necessary 
to  notice  if  it  moves  when  the  patient  swallows. 

The  injections  are  usually  given  twice  a  week,  the  first 
injection  should  not  contain  more  than  0.25  to  0.5  grms. 
tincture  of  iodin,  gradually  increasing  to  1.0  grin,  of  the 
tincture  or  3.0  grms.  iodoform  solution. 

The  action  of  this  treatment  is  usually  very  slow,  it  be- 
ing often  three  or  four  weeks  before  any  improvement  can 
be  noticed.  The  results  are  satisfactory  in  a  large  per- 
centage of  cases  in  struma  follicularis,  but  is  of  no  value 
in  struma  fibrosa.  Gaire  treated  140  cases,  in  90  per  cent 
all  symptoms  of  trachea  stenosis  disappeared.  He  used  a 
solution  of  iodin  1.0  grin. ;  ether,  7.0  ecm. ;  olive  oil,  7.0, 
which  must  be  kept  in  dark-colored  bottles  and  carefully 
stoppered.  Alcohol  injections  have  been  recommended 
by  Schwalbe.  Ergotin,  strychnin,  osmic  acid,  Fowler's 
solution,  1  per  cent  carbolic  spirits,  carbolic  acid,  papain, 
permanganate  of  potash,  ferric  chlorid,  chromic  acid  have 
been  tried  but  with  unsatisfactory  results. 


CHAPTER    VI. 

SURGERY    OF    THE    THYROID    GLAND. 

When  medical  treatment  has  failed  surgical  interfer- 
ence may  become  necessary  under  special  circumstances. 
If  the  dyspnea  is  so  constant  as  to  incapacitate  the  patient 
for  following  active  employment,  or  one  of  a  sedentary 
kind  especially,  such  as  involves  the  bending  of  the  neck 
so  that  the  patient  is  prevented  from  earning  a  living,  and 
if  the  disease  is  progressive  an  operation  should  be  ad- 
vised. Should  there  be  tracheal  stridor  accompanied  by 
a  goitrous  isthmus  or  extension  of  the  swelling  laterally 
or  downward,  there  are  often  sudden  attacks  of  dyspnea, 
which  may  end  fatally  before  assistance  can  be  given. 
These  sudden  attacks  of  dyspnea  are  due  to  some  extra 
exertion  which  calls  into  action  the  additional  muscles  of 
respiration,  the  sternocleidomastoid,  the  sternohyoid  and 
the  sternothyroid,  which,  pressing  on  the  goitre,  produce 
still  further  narrowing  of  the  trachea,  thereby  increasing 
the  dyspnea,  and  as  the  dyspnea  increases  the  action  of 
the  muscles  becomes  still  further  increased,  producing 
closure  of  the  trachea  and  death.  Another  cause  of  sud- 
den enlargement,  increasing  the  dyspnea,  may  be  sudden 
extravasations  of  blood  into  the  goitre. 

In  emergency  it  is  best  to  slit  the  deep  cervical  fascia 
and  to  raise  the  muscles  that  press  upon  the  gland,  allow- 
ing it  to  bulge  forward  away  from  the  trachea;  at  the  same 
time  should  there  be  cyanosis  venesection  should  be  re- 
sorted to.  If  the  foregoing  do  not  give  relief  either  the 
gland  or  isthmus  or  both  must  be  partially  removed,  or 
tracheotomy  performed,  if  the  patient's  condition  will  ad- 
mit of  the  operation.     Tracheotomy  is  often  very  difficult 

100 


SUEGERY    OF    THE    THYROID    GLAND.  101 

under  these  conditions.  Should  the  enlarged  isthmus 
permit  of  the  operation  above  the  gland  there  is  usually 
no  convenient  canula  at  hand,  a  large  rubber  catheter  may 
be  used  or  a  Durham's  canula  with  a  rubber  attachment; 
should  there  be  substernal  enlargement  Konig's  catheter 
should  be  substituted  as  soon  as  possible.  Opening  the 
trachea  below  the  isthmus  is  often  impossible  when  the 
gland  is  much  swollen,  reaching  as  it  often  does  from  the 
cricoid  cartilage  to  the  manubrium.  To  divide  the  isth- 
mus and  then  perform  tracheotomy  is  attended  with  great 
danger  of  hemorrhage  followed  by  septic  pneumonia. 
The  dangers  of  low  tracheotomy  consist  in  the  number  of 
large  vessels,  such  as  the  innominate  artery,  which  may  be 
accidentally  cut,  as  well  as  of  injury  in  the  confined  area 
to  the  dilated  vessels  of  the  gland  itself,  while  the  danger 
of  pneumonia  is  increased.  Should  the  goitre  be  uni- 
lateral it  is  probably  due  to  adenoma  or  cyst ;  in  the  latter 
case  it  may  be  drained  or  removed,  in  the  former  the 
tumor  should  be  enucleated  if  possible,  if  not  the  lobe 
must  be  removed.  Removal  of  the  isthmus  may  not  re- 
lieve the  symptoms.  Should  this  be  the  case  one  lateral 
lobe  should  be  entirely  removed.  It  is  probably  better 
should  the  condition  of  the  patient  permit  to  remove  the 
isthmus  and  one  lateral  lobe  at  once  rather  than  resort  to 
tracheotomy,  as  the  latter  invariably  causes  a  septic 
wound  and  very  often  produces  pneumonia. 

Another  indication  for  operation  is  the  steady  enlarge- 
ment of  the  gland,  with  or  without  dyspnea,  especially  if 
the  enlargement  is  in  the  downward  direction  where  it 
will  become  substernal.  The  lower  the  growth  extends 
the  greater  is  the  danger  of  mediastinal  cellulitis  after 
operation  and  the  less  chance  of  giving  relief  by  tracheot- 
omy in  emergency  cases.  Another  symptom  which  indi- 
cates operative  treatment  is  the  inability  to  stoop  without 
a  sensation  of  blood  to  the  head;  the  inability  to  sleep 


102  THE    THYKOID    AND    PARATHTROID    GLANDS. 

lying  down  so  often  associated  with  asthma,  is  also  a 
serious  symptom.  In  the  first  instance  the  feeling  of  rush 
of  blood  to  the  head  must  be  due  to  pressure  on  the  gland, 
which  in  its  turn  presses  on  the  jugulars,  and  in  the  second 
the  weight  of  the  gland  pressing  upon  the  laryngeal 
nerves  may  be  the  cause  of  the  asthma  and  discomfort, 
"When  the  tumor  is  very  large  there  is  often  a  dragging 
pain  at  the  neck,  sometimes  without  any  other  symptom. 
The  questions  which  the  surgeon  has  to  consider  are  the 
probabilities  of  a  sudden  and  perhaps  fatal  attack  of 
dyspnea,  and  if  the  tumor  is  progressive,  in  both  cases  he 
is  justified  in  advising  operation  after  fully  weighing  the 
dangers  of  the  operation,  which  are  increased  under  the 
following  conditions: 

If  the  goitre  is  very  large,  and  especially  if  it  is  fixed  on 
a  broad  base,  if  the  goitre  is  calcified,  or  if  its  limits  are 
indistinctly  defined,  the  risks  of  operation  are  materially 
increased.  In  those  cases  which  are  substernal  the  risk  of 
mediasternal  cellulitis  is  great.  The  age  of  the  patient  is 
also  of  moment,  Billroth  being  of  opinion  that  no  opera- 
tion should  be  performed  after  the  age  of  forty  unless 
there  is  malignant  disease,  and  as  malignant  disease  only 
attacks  unhealthy  glands  he  would  operate  early.  On  no 
account  should  the  operation  be  performed  for  the  sake 
of  the  personal  appearance  only  above  this  age,  but  in 
early  adolescence  when  the  gland  is  not  very  large,  it  is 
permissible  for  fear  of  future  dyspneic  symptoms  or 
malignant  growth.  Patients  with  feeble  pulse,  which  is 
the  result  of  pressure  on  the  veins  and  trachea  and  from 
the  intervention  of  a  more  or  less  voluminous  vascular  net- 
work producing  strain  on  the  heart,  are  apt  to  succumb  to 
the  operation. 

There  are  a  number  of  cases  which  appear  to  be  allied 
to  Basedow 's  disease  but  which  have  not  the  typical  symp- 
toms and  are  to  be  operated  upon  with  caution,  there  being 


SURGERY    OF    THE    THYROID    GLAND.  103 

greater  risk  of  excessive  action  of  the  heart,  pyrexia,  and 
perhaps  lung  trouble.  These  cases  are  usually  young  pa- 
tients with  a  soft  parenchymatous  goitre  affecting  the 
whole  gland,  with  marked  vascularity,  pulsation,  a  pulse 
of  90  or  more,  the  heart  easily  excited,  with  a  soft  systolic 
bruit.  These  are  cases  which  are  suffering  from  hyper- 
thyroidea,  and  are  distinct  from  other  forms  of  goitre. 
After  the  operation  the  patient  is  restless  and  depressed, 
there  is  a  constant  effort  to  clear  the  throat  by  coughing, 
which  disturbs  the  wound ;  he  feels  a  dread  of  suffocation 
from  the  accumulation  of  mucus  in  the  trachea  and  larger 
bronchial  tubes ;  the  pulse  runs  up  to  120  or  130,  the  tem- 
perature rises,  which  is  followed  by  exhaustion  and  death. 
Should  the  patient  survive  the  wound  does  not  heal  by 
primary  union,  there  is  a  profuse  blood-stained  discharge 
for  several  days,  though  it  may  not  be  infected.  These 
symptoms  are  not  uncommon  after  operation  for  Base- 
dow's disease  and  are  probably  the  result  of  a  quantity  of 
colloid  substance  having  been  expressed  out  of  the  gland 
during  the  operative  manipulations.  Great  care  must  be 
exercised  in  handling  the  gland  so  as  to  prevent  pressure 
causing  the  exudation  of  the  colloid  substance,  and  the 
wound  washed  out  with  sterilized  water.  It  is  well  to 
place  some  absorbent  cotton  in  the  wound,  renewing  it 
every  two  or  three  hours  so  as  to  prevent  any  further 
exudation  from  entering  the  system.  If  this  is  attended 
to  the  symptoms,  which  are  those  of  thyroidismus,  will 
disappear. 

In  case  of  partial  extirpation  or  enucleation  the  wound 
usually  heals  well  and  the  respiratory  symptoms  are  re- 
lieved, the  constricted  trachea  returning  to  normal  in  a 
short  time.  Should  there  have  been  paresis  of  the  laryn- 
geal nerves  from  pressure  of  the  goitre  and  consequent 
failure  of  the  voice  there  will  usually  be  a  return  to  normal. 
Kronlein  found  that  out  of  25  cases  of  inhibition  of  the 
vocal  cords  21  returned  to  normal  after  the  operation. 


104  THE    THYROID    AND    PARATHYROID    GLANDS. 

The  operation  for  the  removal  of  goitre  was  for  a  long 
time  considered,  and  not  without  reason,  as  being  one  of 
the  most  dangerous  attempted,  but,  thanks  to  antisepsis 
and  asepsis,  special  technique  and  the  recognition  of  the 
cause  of  tetany  and  cachexia  strumipriva,  which  at  first 
so  often  followed  the  operation,  the  mortality  in  the  hands 
of  good  operators  has  fallen  to  almost  nil.  Billroth,  of 
Vienna,  and  Kocher,  of  Berne,  have  been  the  two  surgeons 
to  whom  is  due  this  most  satisfactory  result.  Kocher  had 
no  mortality  in  272  consecutive  cases,  Kronlein  in  200, 
Roux  in  526  operations  had  a  mortality  of  1.27  per  cent ; 
v.  Mikulicz  in  151  2.6  per  cent;  v.  Bruns  a  mortality  of 
2.0  per  cent.  Riverdin  collected  the  statistics  and  found 
that  in  6103  operations  the  mortality  was  2.88  per  cent. 
Eiverdin  also  gives  the  statistics  of  93  cases  of  death  from 
the  operation,  42  being  from  suffocation,  asphyxia  or  pneu- 
monia, 19  from  hemorrhage,  13  from  wound  infection,  9 
from  shock  and  wounding  of  the  recurrent  laryngeals,  6 
from  heart  syncope  and  4  from  tetany  or  myxedema. 

The  most  dangerous  complication  during  operation  is 
hemorrhage,  which  can  be  guarded  against  by  a  sufficiently 
large  incision,  adequate  retraction  or  division  of  the  over- 
lying muscles,  and  by  identifying  the  capsule.  The  latter 
is  often  difficult,  the  layers  of  the  deep  cervical  fascia  over 
the  tumor  vary  in  thickness  and  number,  each  one  must  be 
divided  carefully  till  the  tumor  is  reached,  which  can  be 
recognized  by  its  purple  red  color,  its  consistency  and  the 
way  the  vessels  stand  out  and  ramify  over  the  surface. 
The  arteries  are  usually  easy  to  manage  but  the  veins  give 
great  trouble,  being  very  numerous,  thin-walled  and  are 
met  at  every  step  of  the  operation.  When  the  growth  is 
soft  as  well  as  vascular  any  opening  of  the  capsule  is  apt 
to  flood  the  wound  with  blood,  making  it  difficult  to  find 
the  bleeding  point,  increasing  the  danger  of  including  the 
nerves  within  the  ligature.     Asphyxia  and  aphonia  may 


SUKGEEY    OP    THE    THYKOID    GLAND.  105 

occur  from  including  a  recurrent  laryngeal  nerve  within  a 
ligature,  cutting  the  nerve  or  bruising  it.  Aphonia  may 
be  the  result  of  wounding  the  inferior  laryngeal  or  drag- 
ging on  it;  possibly  section  of  the  cricothyroid  branch  of 
the  superior  laryngeal  nerve  may  also  produce  aphonia. 
Months  after  the  operation  these  symptoms  may  appear, 
owing  to  inclusion  of  the  inferior  laryngeal  nerves  in  the 
cicatrix.  There  is  also  a  progressive  ascending  neuritis 
of  these  nerves  which  may  have  commenced  anterior  to 
the  operation,  due  to  compression  of  the  goitre.  When 
the  growth  is  large  or  when  fixed  by  adhesions  or  attached 
by  a  broad  base  the  nerves  are  apt  to  be  injured ;  also  when 
the  tumor  is  ill-defined  or  encircles  the  trachea  and  eso- 
phagus closely,  as  it  usually  does  when  the  disease  is 
malignant. 

Even  after  every  care  postoperative  hemorrhage  is  not 
uncommon  so  that  it  is  requisite  that  the  patient  be  care- 
fully watched,  any  change  of  color  or  weakness  of  pulse 
calling  for  immediate  examination.  The  venous  hemor- 
rhage is  possibly  even  more  dangerous  than  the  arterial, 
owing  to  the  possible  formation  of  air  emboli,  which  may 
cause  sudden  death,  the  veins  in  the  neighborhood  of  the 
operation  being  without  valves  and  the  vessels  dilated. 
Treves  recommends  washing  with  normal  salt  solution  and 
leaving  it  in  the  wound,  so  that  it  will  be  aspirated  into 
the  jugular  instead  of  air.  Should  the  recurrent  laryngeal 
nerves  be  accidentally  cut  during  the  operation  paralysis 
of  the  vocal  cords  will  follow.  Wounding  of  the  superior 
laryngeal  nerves  and  of  the  sympathetic  has  to  be  guarded 
against.  In  the  first  case  anesthesia  of  the  lining  mem- 
brane of  the  larynx  will  ensue.  Wounding  of  the  sympa- 
thetic produces  postoperative  ptosis,  one-sided  widening 
of  the  pupil  and  sinking  of  the  eyeball.  In  a  case  in  Bill- 
roth's  clinic  there  was  narrowing  of  the  pupil,  a  differ- 
ence of  temperature  between  the  right  and  left  side  of  the 


106  THE    THYROID    AND    PAEATHYEOID    GLANDS. 

face,  congestion  and  heat  on  the  operated  side,  combined 
with  heavy  sweating  and  increased  secretion  of  the  saliva. 
Should  the  hypoglossal  nerve  be  injured  paralysis  and 
atrophy  of  one  half  of  the  tongue  will  occur. 

The  most  dangerous  of  the  postoperative  complications 
is  infection  of  the  wound,  which  may  result  from  faulty 
technique;  from  the  vomiting  of  the  patient  into  the 
wound,  or  from  wounding  of  the  esophagus.  Should  it 
have  been  necessary  to  perform  tracheotomy  the  proba- 
bilities of  infection  are  very  great.  In  many  cases  death 
follows  rapidly  on  infection,  which  may  extend  into  the 
mediastinum,  causing  dyspnea,  severe  pain  under  the 
manubrium  sterni,  pain  on  pressure,  sweating  and  high 
fever.  The  wound  must  be  at  once  thoroughly  opened 
and  cleaned.  Hyperthermia  to  about  38  degrees  C.  is 
common  in  thyroid  operations.  Bergeat  observed  it  on  all 
but  three  out  of  249  operations,  other  surgeons  observed 
it  in  from  60  to  80  per  cent  of  their  cases.  It  seems  prob- 
able that  this  hyperthermia  is  the  result  of  the  gland  being 
squeezed  during  the  operation,  causing  exudation  of  col- 
loid and  is  really  the  result  of  hyperthyroidea.  Some- 
times there  is  very  difficult  breathing  after  the  operation, 
which  may  be  due  to  too  tight  bandaging,  too  much  tam- 
pon in  the  wound,  to  postoperative  hemorrhage,  which, 
by  producing  a  large  hematoma,  may  press  on  the  trachea 
or,  in  cases  of  tracheotomy,  bleeding  into  the  trachea.  In 
other  cases  there  is  an  accumulation  of  mucus,  which  re- 
quires that  the  pharynx  be  washed  out  with  the  head 
hanging  downward;  this  complication  predisposes  to 
pneumonia.  Occasionally  the  trachea  may  kink  through 
some  sudden  movement  of  the  head. 

A  complication  which  is  to  be  dreaded  is  pneumonia, 
which  may  develop  very  quickly,  when  it  is  probably 
caused  by  venous  sepsis.  As  a  rule,  however,  it  develops 
slowly  during  the  first  few  days  after  operation ;  paralysis 


SUKGEEY    OF    THE    THYEOID    GLAND.  107 

of  the  larynx  through  injury  of  the  recurrent  laryngeal 
nerves  is  a  predisposing  cause,  as  during  sleep  the  glottis 
is  open,  the  saliva  and  mucus  from  the  mouth  flows  into 
the  trachea.  Wolfler  injected  human  saliva  into  the 
trachea  of  rabbits,  but  failed  to  produce  pneumonia;  on 
the  other  hand,  if  infected  substances  were  injected  lob- 
ular pneumonia  followed.  Difficulty  and  pain  on  swal- 
lowing is  usual  for  the  first  few  days  after  operation,  when 
it  gradually  disappears. 

The  administration  of  an  anesthetic  is  a  point  which  re- 
quires much  discretion  and  is  still  debatable.  The  danger 
of  excitement  at  the  commencement  of  anesthesia  increas- 
ing the  respiratory  disturbance  causing  risk  of  as- 
phyxia has  to  be  borne  in  mind ;  often  the  condition  of  the 
lungs  from  chronic  catarrh  or  emphysema,  as  well  as  dila- 
tation of  the  right  heart,  cause  the  surgeon  the  greatest 
anxiety.  The  venous  stasis,  already  severe,  will  be  in- 
creased, while  vomiting  may  cause  sudden  death.  Many 
operators  use  no  anesthetic,  on  the  ground  that  the  hand- 
ling of  the  goitre  is  almost  painless,  the  pain  being  only  at 
the  first  incision  and  the  luxation  of  the  tumor;  others 
use  cocain,  Schleich  infiltration  or  other  methods  of  local 
anesthesia.  In  some  few  emergency  cases  patients  are 
brought  to  the  table  in  a  semiasphyxiated  condition,  when 
the  danger  of  anesthesia  is  so  great  that  the  surgeon  will 
be  compelled  to  operate  either  with  local  anesthesia  or 
with  none,  but  these  are  few  and  far  between.  In  any  case 
the  patient  must  be  placed  in  the  position  in  which  the 
difficulty  of  breathing  is  least,  which  the  patient  is  usually 
able  to  explain,  and  may  be  either  sitting  or  extended; 
the  head  should  be  firmly  fixed  so  as  to  prevent  any  sudden 
motion.  A  bolster  is  placed  under  the  neck  and  the  hands 
held  by  an  assistant.  Every  care  must  be  taken  not  to 
excite  the  patient.  There  should  be  a  protector  placed  be- 
tween the  face  and  the  field  of  operation  to  prevent  infec- 


108  THE    THYEOID    AND    PAEATHYEOID    GLANDS. 

tion  from  the  saliva  or  from  the  patient  vomiting  into  the 
wound. 

The  parts  having  been  prepared,  the  head  and  shoulders 
conveniently  supported  and  secured  against  movement, 
a  free  incision  is  made  along  the  anterior  border  of  the 
sternocleidomastoid  over  the  most  prominent  portion  of 
the  tumor,  avoiding  large  veins.  An  ample  longitudinal 
incision  will  usually  be  sufficient  and  leave  little  noticeable 
disfigurement,  as  the  scar  will  fall  into  the  sulcus  internal 
to  the  muscle.  It  is  rarely  necessary  to  make  more  than 
the  longitudinal  incision.  The  skin  and  platysma  are  cut, 
the  superficial  veins  tied,  the  deep  fascia  divided,  and  the 
hyoid  depressors  separated  or  divided.  If  necessary  the 
patient  will  usually  begin  to  breathe  more  easily.  It  is  of 
importance  that  the  opening,  both  in  the  skin  and  in  the 
fascia,  should  be  ample,  giving  plenty  of  room  to  prevent 
the  squeezing  of  the  gland,  which  may  cause  the  serious 
consequences  mentioned  above.  The  goitre  on  being  laid 
bare  can  be  recognized  by  its  blue  red  color  and  large 
veins,  which  stand  out  as  they  ramify  over  the  surface  of 
the  gland. 

The  sternomastoid  is  retracted,  drawing  out  the  large 
vessels,  then  with  his  finger  or  blunt  scissors  the  surgeon 
frees  the  tumor  from  its  bed,  shelling  it  forward,  probably 
finding  that  it  is  only  fixed  above,  below  and  internally. 
Care  must  be  taken  to  work  gently  and  to  keep  close  to 
the  tumor.  As  the  veins  are  distended  and  the  walls  thin 
great  care  must  be  exercised  not  to  injure  them,  and  on 
no  account  must  the  capsule  be  broken.  Should  this  occur 
the  wound  is  at  once  flooded  with  blood.  The  upper  ex- 
tremity is  freed  first,  the  superior  vessels  ligated,  either 
doubly  with  chromic  gut  passed  with  an  aneurysm  needle 
or  divided  between  two  pairs  of  forceps,  both  ends  being- 
tied.  The  tumor  must  be  isolated  in  a  downward  direc- 
tion and  any  portions  which  may  exist  under  the  sterno- 


SURGERY    OF    THE    THYROID    GLAND. 


109 


mastoid  muscle  turned  out.  It  is  better  to  now  divide  the 
isthmus,  which  can  be  done  either  by  double  ligature  after 
transfixing  with  an  aneurysm  needle  carrying  strong  gut 
or  it  may  be  torn  through  and  each  bleeding  point  tied. 
If  it  should  be  very  vascular  and  large  it  should  be  subdi- 
vided and  tied  in  several  places,  the  ligatures  interlock- 
ing ;  it  may  be  seared  through  with  the  cautery  or  by  an 
ecraseur,  the  stump  should  then  be  treated  with  zinc 
chlorid  or  formalin,  packed  with  sterilized  gauze  and 
brought  outside  the  wound.  The  tumor  is  now  drawn  to 
one  side  and  the  inferior  vessels  dissected  out ;  as  the  re- 
current laryngeal  nerve  runs  along  with  the  inferior  thy- 
roid artery  when  near  the  gland  the  artery  should  be 
ligatured  as  near  the  axis  as  possible  always  examining 
carefully  to  be  sure  that  the  nerve  is  not  included  in  the 
ligature.  After  the  gland  is  removed  all  bleeding  points 
must  be  stopped  and  the  wound  thoroughly  dried  out. 

The  wound  even  after  removal  of  one  lobe  only  is  often 
very  large  and  deep,  the  larynx,  trachea,  esophagus  and 
large  vessels  all  being  exposed,  as  well  as  the  dome  of  the 
pleura,  and  is  difficult  to  drain  properly,  as  it  dips  below 
the  clavicle.  In  parachymatous  cases,  where  the  opera- 
tion has  been  easy  and  the  parts  little  disturbed,  the  sur- 
geon will  dispense  with  draining  and  trust  to  a  dry  wound 
and  carefully  applied  pressure.  The  edges  should  be 
exactly  brought  into  position  to  promote  easy  healing. 
The  scar  may  become  keloid,  but  this  is  only  temporary,  a 
white  scar  being  the  only  disfigurement.  The  dressing  in 
immediate  contact  with  the  wound  should  press  evenly, 
distributing  the  discharge  over  a  large  surface  of  dress- 
ings and  obliterating  the  cavity.  In  order  to  keep  the 
dressings  in  position  the  bandage  should  be  passed  under 
the  axilla?,  using  a  pad,  and  then  wound  round  the  chin  and 
forehead  and  made  secure  with  stitching;  this  prevents 
the  bandage  slipping  and  exposing  the  upper  half  of  the 


110 


THE    THYROID    AND    PARATHYROID    GLANDS. 


wound.  Under  the  chin  should  be  a  protector  to  prevent 
the  dressings  being  soiled  by  the  saliva,  etc.  Should, 
however,  the  parts  be  much  disturbed  during  the  opera- 
tion drainage  is  advisable.  In  cases  where  there  may  be 
exudation  of  thyroid  secretion  the  sutures  may  be  left  long 
and  untied,  the  wound  plugged  with  sterilized  gauze,  and 
after  a  few  days  the  gauze  may  be  removed  and  the  su- 
tures tightened. 

Tracheotomy  should  never  be  performed  except  in  most 
urgent  cases,  as  the  results  are  almost  always  fatal  from 
septic  infection  of  the  wound,  septic  bronchopneumonia 
and  partly  from  increased  shock.  If  apparently  needed 
the  surgeon  should  first  divide  the  fascia  and  muscles  and 
endeavor  to  ease  the  pressure  by  letting  the  tumor  bulge 
forward.  The  tracheotomy  wound  requires  great  care 
and  attention;  the  wound  must  be  left  open  and  washed 
with  bichlorid  1  to  4000  very  frequently,  but  in  spite  of  all 
precautions  septic  infection  will  ensue. 


Fig.  29. — Struma  Vasculosa. 


Fig.  30. — Adenoma  of  Thvroid. 


Enucleation  of  thyroid  adenomata  has  been  advocated 
by  Porta,  Billroth,  Socin,  Eiverdin,  Wolfler,  on  the  ground 
that  there  is  less  danger  of  wounding  the  nerves  and  hem- 
orrhage, and  also  that  there  is  certain  to  be  enough  active 
thyroid  tissue  left  to  prevent  tetany  or  cachexia  strumi- 


STJRGEKY    OF    THE    THYKOID    GLAND.  Ill 

priva.  As  early  as  1804  Briininghausen  enucleated  a 
cyst;  in  188-4  Billroth  had  performed  8  operations  suc- 
cessfully. 

In  ordinary  cases  of  solid  enlargement  of  the  thyroid 
encapsulated  adenomata  are  often  present,  which  can  be 
comparatively  easily  enucleated,  and  is  a  much  less  severe 
operation  than  the  partial  removal  of  the  gland.  The 
incision  is  the  same  as  in  the  partial  removal,  the  fascia 
being  divided  in  the  same  way.  On  the  gland  being  ex- 
posed it  is  necessary  to  examine  and  palpate  carefully  in 
order  to  define  accurately  the  limitations  of  the  capsule  of 
the  adenoma.  Usually  it  is  easily  recognized,  rarely  the 
side  of  the  gland  will  have  to  be  raised  and  explored.  The 
adenomata  can  be  recognized  by  its  smooth  white  cover- 
ing. Adenomata  may  be  multiple,  in  which  case  each 
must  be  enucleated  separately,  or  those  left  behind  will 
continue  to  grow  and  necessitate  a  second  operation. 
After  enucleation  the  gland  does  not  shrink  so  completely 
or  permanently  as  after  the  extirpation  of  one  lobe  and 
half  the  isthmus.  The  operation  of  enucleation  is  not 
applicable  to  the  gelatinous  form  and  should  never  be 
tried  unless  the  adenoma  can  be  distinctly  defined.  It  is 
rare  that  cysts  or  adenomata  occur  in  bilateral  goitres, 
they  being  usually  unilateral.  Patients  suffering  from 
unilateral  goitres  rarely  seek  operation,  as  the  dyspnea  is 
not  severe.  On  the  whole  partial  removal  of  the  gland  is 
preferable,  giving  better  results  and  less  probability  of  a 
return. 

Eemoval  of  the  isthmus  alone  is  often  followed  by 
shrinkage  of  the  tumor  and  has  the  advantage  of  requiring 
less  preparation,  enabling  the  surgeon  to  give  relief  in 
emergency  cases,  when  the  slitting  of  the  skin,  muscles 
and  fascia  has  failed  to  give  relief  without  much  assist- 
ance. It  is  preferable  in  cases  of  very  large  growth, 
when  anesthesia  is  dangerous  and  time  is  short,  or  when 


112  THE    THYEOID    AND    PABATHYEOID    GLANDS, 

the  enlargement  of  the  isthmus  is  the  cause  of  the  tracheal 
stridor. 

In  cases  of  malignant  disease  the  dangers  of  the  opera- 
tion are  much  increased,  as  the  growth  hugs  the  trachea, 
dipping  into  the  sulci  between  the  large  vessels  and  the 
trachea,  infiltrating  important  parts,  often  growing  into 
the  mediastinum.  Under  these  conditions  the  probabili- 
ties of  wounding  the  nerves  and  vessels  are  very  much 
increased. 

Another  form  of  operation,  which  has  recently  been 
advocated  and  practiced  with  success,  is  ligature  of  the 
arteries  of  the  gland,  leaving  the  tumor  in  situ.  This 
operation  has  given  contradictory  results,  splendid  results 
being  opposed  by  utter  failures.  The  failures  are  due  to 
the  existence  of  abnormal  arteries,  as  if  all  arteries  are 
tied  the  circulation  must  cease,  and  the  gland  atrophy, 
but  if  the  circulation  is  not  cut  off  or  reestablishes  itself 
the  operation  will  fail.  Experience  has  shown  that  liga- 
ture of  all  the  arteries  does  not  produce  gangrene. 

The  difficulties  of  the  operation  consist  in  the  finding 
of  the  arteries,  they  varying  much  in  position,  in  that  the 
vessels  are  often  diseased  and  in  that  the  nerves  are  apt 
to  be  ligated  with  the  vessels.  The  landmarks  for  the 
arteries  are  as  follows: 

The  superior  thyroid,  the  first  branch  of  the  external 
carotid,  arises  just  above  the  bifurcation  of  the  common 
carotid  about  one-quarter  of  an  inch  below  the  great  cornu 
of  the  hyoid  bone,  covered  at  first  only  by  thin  fascia  and 
the  platysma,  it  ascends  slightly  and  then  curves  down- 
ward, taking  a  tortuous  course  covered  by  the  depressors 
of  the  hyoid  bone  and  the  sternothyroid. 

The  head  should  be  raised  and  turned  to  the  opposite 
side;  the  incision  is  made  along  the  inner  border  of  the 
sternomastoid  muscle,  with  its  centre  corresponding  to 
the  upper  border  of  the  thyroid  cartilage,  the  sternomas- 


SUKGERY    OF    THE    THYROID    GLAND.  113 

toid  and  large  vessels  are  drawn  outward  and  the  omo- 
hyoid downward  and  inward,  and  the  artery  sought  for  in 
the  hollow  between  the  larynx  and  the  carotid.  Usually 
there  are  also  present  some  enlarged  veins  of  superior 
thyroid  which  will  also  require  ligatures. 

The  inferior  thyroid  is  more  difficult  to  find.  It  is  the 
largest  branch  from  the  thyroid  axis  of  the  subclavian, 
ascending  tortuously  inward  behind  the  carotid  sheath, 
the  middle  cervical  ganglion  lying  in  front  of  it.  Before 
entering  the  gland  it  runs  a  short  distance  in  close  relation 
with  its  posterior  surface,  and  the  recurrent  laryngeal  is 
then  in  contact  with  it,  often  passing  between  the  terminal 
branches  of  the  artery ;  further,  the  left  artery  is  often  in 
close  contact  with  the  esophagus,  while  the  thoracic  duct, 
at  first  posterior,  arches  over  the  artery  on  this  side  to 
enter  the  subclavian  vein.  The  tubercle  of  Chassaignac 
or  the  transverse  process  of  the  sixth  cervical  vertebra  and 
the  body  of  the  fifth  vertebra  are  landmarks  for  the  point 
at  which  the  artery  enters  the  gland. 

The  incision  is  made  along  the  anterior  border  of  the 
sternocleidomastoid  to  the  clavicle,  as  if  to  ligate  the  caro- 
tid low  down,  the  fascia  divided,  the  sternomastoid  and 
the  carotid  sheath  and  contents  drawn  out.  The  head  is 
then  flexed  to  relax  the  carotid,  the  tubercle  felt  for  and 
the  artery  sought  for  below,  working  with  a  director,  the 
vessel  exposed  and  then  ligated.  Great  care  has  to  be 
exercised  as  the  artery  is  often  degenerated  and  friable 
from  pressure,  and  in  order  to  avoid  the  nerve  it  is  as 
well  to  ligate  as  close  to  the  carotid  as  possible.  The 
presence  of  the  phrenic  nerve  has  also  to  be  borne  in  mind. 
•  This  operation  seems  especially  useful  in  Basedow's 
disease. 

Cysts  of  the  gland,  though  usually  only  unilateral,  may 
grow  to  a  great  size  and  require  removal.  Occasionally 
the  injection  of  ferric  chlorid  gives  good  results,  but  there 


114  THE    THYROID    AND    PARATHYROID    GLANDS. 

is  a  risk  of  suppuration  and  cellulitis.  Should  the  cyst 
not  be  of  any  very  great  size  it  may  be  excised,  it  turns 
out  easily  if  it  has  not  been  previously  blistered,  when 
adhesions  usually  exist. 

If  convenient  it  may  be  emptied  first  and  then,  by 
squeezing  the  edges,  turned  out  empty.  After  such  an 
operation  the  lobe  appears  to  be  useless,  but  should  on 
no  account  be  removed  but  bandaged  in  such  a  way  as  to 
apply  even  but  not  excessive  pressure.  Should  the  cysts 
be  multiple  the  whole  lobe  must  be  removed. 

If  excision  is  impossible  incision  must  be  practiced. 

Clean  up  the  operating  field  and  cut  down  as  previously 
described,  carefully  securing  all  bleeding  points,  slit  open 
the  cyst  and  examine.  The  contents  may  be  either  gelat- 
inous or  grumous,  serous,  mucoid  or  coagulable  blood 
clot.  On  examination  the  wall  of  the  cyst,  if  of  long 
standing,  may  be  so  fibrous  and  evascular  that  sloughing 
may  take  place;  on  the  other  hand,  it  may  be  vascular. 
Should  any  of  the  vessels  be  wounded  very  suddenly, 
leaving  no  time  for  suturing,  it  will  be  necessary  to  plug 
at  once.  These  cysts  are  difficult  to  heal  from  the  bottom, 
the  edge  of  the  slit  may  be  sewed  to  the  skin,  the  inside 
curetted  and  packed  lightly. 

In  all  these  operations  there  is  very  considerable  risk 
from  hemorrhage,  from  infection,  from  exudation  of  the 
colloid  substance  from  the  gland,  from  injury  to  the 
nerves  and  vessels,  as  well  as  the  danger  of  asphyxia 
during  anesthesia.  As  shown  above  the  mortality  from 
the  operations  is  not  large.  Riverdin  collected  the  mor- 
tality of  the  various  operations,  which  are : 

Percent 
Mortality. 

Intraglandular  enucleation    0.78 

Combined  enuclear  resection  2.99 

Partial  extirpation   3.46 

Resection  according  to  v.  Mikulicz 6.66 


SURGERY    OF    THE    THYROID    GLAND.  115 

There  are  two  diseases  which  occasionally  follow  the 
complete  excision  of  the  thyroid  gland,  or  if  a  sufficient 
quantity  of  active  gland  substance  is  not  left  in  situ. 

As  early  as  1818  Ch.  Jong  and  in  1833  Langenbeck  ob- 
served spasms  occur  after  the  total  excision  of  the  thyroid 
gland;  in  Billrot's  clinic  between  1870  and  1880  the  dis- 
ease was  observed  about  forty  times  after  operation. 

The  disease  exhibits  itself  in  tetanic  spasms,  somewhat 
resembling  tetanus,  which  occur  not  only  in  the  extremi- 
ties, but  also  in  the  muscles  of  the  larynx  and  diaphragm, 
soon  causing  death.  The  convulsions  are  of  two  grades 
of  intensity,  which  may  occur  in  the  same  case,  the  lighter 
ones  occurring  in  the  early  stages,  increasing  in  severity 
as  the  disease  nears  its  termination.  Sometimes  the  con- 
vulsions appear  immediately  after  the  operation,  at  others 
not  till  ten  days  later.  Usually  there  are  premonitory 
symptoms  of  an  attack,  consisting  of  a  feeling  of  uneasi- 
ness and  stiffness,  with  a  weakness  in  the  muscles  of  the 
forearms  and  the  calves  of  the  legs;  rarely  there  are  no 
premonitory  symptoms,  the  attack  coming  on  with  great 
suddenness.  In  many  cases  it  is  possible  to  predict  a 
tetanic  condition  before  the  first  spasm,  from  the  feeling 
of  numbness,  etc.,  and  more  especially  from  the  Chvostek 
and  Trousseau  phenomena.  The  first  consists  in  very 
rapid  sucking  movements,  which  are  produced  by  light 
taps  on  the  facial  nerve  as  it  leaves  the  parotid  gland. 
The  second  and  by  far  the  most  important  of  the  two  is 
that  in  a  few  minutes  after  pressure  on  an  artery  or  nerve 
a  convulsion  of  the  part  which  they  supply  is  produced. 
Chvostek 's  sign  is  so  easily  carried  out,  being  without  any 
danger  or  discomfort  to  the  patient,  that  it  should  be 
always  tried  after  total  extirpation  of  the  gland.  Trous- 
seau's sign  is  not  without  danger,  as  the  muscle  convul- 
sions which  it  produces  may  be  very  severe.  The  convul- 
sions usually  begin  in  the  calves  of  the  legs  and  with  a 


116 


THE    THYEOID    AND    PARATHYROID    GLANDS. 


feeling  of  numbness  in  the  face ;  in  light  spasms  the  con- 
vulsions are  usually  confined  to  the  upper  extremities, 
seldom  occurring  in  the  lower  extremities  at  the  same 
time;  the  position  of  the  joints  of  the  hand  and  fingers 
suggest  irritation  of  the  ulnar  nerve,  the  arm  is  slightly 
bent  at  the  elbow  and  flexed  toward  the  ulnar  side,  the 


Fig.  31. — Cachexia  strumipriva  in  a  girl  26  years  old.      (v.  Brans.) 

fingers  bent  at  the  metacarpophalangeal  joint,  the  inter- 
phalangeal  joint  is  straight  and  the  thumb  in  the  palm  of 
the  hand,  as  in  the  typical  writer's  or  mid- wife's  hand. 
This  is  the  most  common  position;  in  other  cases  the 
fingers  are  extended  wide  apart  or  the  fist  is  closed,  with 
the  thumbs  between  the  index  and  middle  finger.  The 
muscles  of  the  forearm  are  hard  and  tense  to  the  touch; 
it  is  difficult  to  move  the  joints  of  the  hand  or  fingers 


SURGERY    OF    THE    THYROID    GLAND.  117 

during  the  spasm;  they  immediately  return  to  their  for- 
mer position.     In  the  majority  of  cases  the  spasms  of  the 
upper  extremity  are  accompanied  by  the  lower,  which  con- 
sist of  stretching  of  the  hip  and  knee  with  plantar  flexion, 
the  tendons  drawn  to  the  sole  of  the  foot,  while  the  severest 
strain  is  on  the  calves.     The  expression  of  the  face  shows 
intense  pain,  there  is  profuse  sweating,  the  temperature 
may  rise  a  little,  the  pulse  rate  be  increased.     The  spasms 
last  from  two  or  three  minutes  to  a  quarter  of  an  hour  or 
more  and  occur  several  times  in  the  day  or  one  each  day, 
or  on  alternate  days.     The   sensorium  is   always  free. 
Sometimes  there  is  edematous  swelling  of  the  extremities. 
The  severer  forms,  which  usually  begin  with  a  light 
spasm  and  slowly  or  rapidly  progress  in  intensity,  may 
last  in  spite  of  medication  for  days  with  hardly  any  ap- 
preciable break.     In  these  cases  there  is  also  contraction 
of  the  muscles  of  the  face,  they  become  fixed,  the  mouth 
resembling  that  of  a  fish.      The  abdominal  muscles  are 
also  severely  contracted,  the  recti  standing  out  like  strands 
of  steel.     The  tonic  spasms  of  the  back  often  produce  opis- 
thotonos.     When  the  spasms  attack  the  diaphragm  the 
respiration  comes  to  a  standstill,  in  expiration  followed  by 
severe  dyspnea.      The  contraction  of  the  muscles  of  the 
neck  produces  cyanosis.      The  patients  suffer  from  great 
pain  as  well  as  from  air  hunger,  sometimes  shrieking,  in 
other  cases  this  is  impossible,  owing  to  spasm  of  the  mus- 
cles of  the  larynx,  articulation  may  be  possible  at  short 
quick  intervals,  when  the  same  word  may  be  repeated  each 
time.      Swallowing  is  also  impossible,  so  that  only  small 
quantities  of  fluid  can  be  given.     As  the  end  approaches 
the  patient  becomes  comatose  and  the  spasms  cease,  only 
to  commence  again  when  he  is  aroused  from  the  coma. 
Death  rarely  supervenes  during  the  height  of  the  spasms, 
but  hours  or  days  after  they  have  subsided. 

The  microscopical  findings  are  negative,  twice  Weis 


]  18  THE    THYEOID    AND    PAEATHYKOID    GLANDS. 

f  oimcl  slight  infiltration  of  the  gray  matter  of  the  anterior 
horn  of  the  medulla. 

From  the  experiments  on  the  extirpation  of  the  thyroid 
and  parathyroid  glands  recorded  above,  it  is  probable  that 
the  tetanic  convulsions  after  total  excision  of  the  gland 
are  due  to  the  parathyroids  having  been  included  in  the 
tissue  excised,  especially  as  cases  of  tetany  have  occurred 
where  there  was  apparently  sufficient  active  thyroid  tissue 
left  in  situ  to  prevent  the  patient  suffering  from  athy- 
roidea;  in  the  latter  case  the  parathyroids  have  either 
been  injured  before  or  during  the  operation  or  have  been 
completely  removed.  It  is  probable  that  operative  tetanic 
thyropriva  will  be  very  rarely  seen  in  the  future,  surgeons 
being  fully  alive  to  the  importance  not  only  of  leaving 
sufficient  thyroid  substance  but  also  the  parathyroids. 
Should  a  case  occur  the  treatment  consists  in  thyroid  and 
parathyroid  feeding,  but  the  prognosis  is  very  unfavor- 
able. 

Cachexia  strumipriva  is  really  a  myxedema  produced 
by  the  removal  of  the  thyroid  gland,  either  totally  or  par- 
tially, by  operation.  In  1867  Sick  removed  a  goitre  from 
a  ten-year-old  boy,  who  was  at  the  time  of  the  operation 
of  average  mentality ;  shortly  after  the  operation  the  boy 
became  stupid  and  gradually  cretinic.  In  1883  Riverdin 
and  Kocher  both  published  their  observations  of  a  cretinic 
condition  supervening  after  removal  of  the  gland. 

The  disease,  unlike  tetany,  does  not  appear  till  some- 
times weeks  or  months  after  the  operation,  and  exhibits 
itself  in  a  loss  of  mentality,  in  a  chronic  edema  of  the  skin, 
and  if  the  operation  has  been  performed  in  youth  the 
growth  of  both  mind  and  body  ceases  from  that  time  on. 
At  first  there  is  only  apathy  and  loss  of  energy  observed, 
but  later  there  is  a  decided  loss  of  intelligence,  the  mem- 
ory becomes  poor,  finally  progressing  to  a  complete 
apathy,   out   of  which   it  is   impossible   to    arouse   him. 


SURGERY    OF    THE    THYROID    GLAND.  119 

Tetany  is  rarely  present,  but  the  sensibility  is  reduced. 
In  some  cases  the  mentality  is  not  much  affected  though 
the  skin  changes  occur,  rendering  the  diagnosis  easy. 

The  skin  of  the  face  becomes  thickened,  white,  waxlike, 
rough  and  dry,  the  sweat  and  sebaceous  glands  ceasing  to 
functionate ;  the  hair  becomes  white  and  falls  out,  the  ex- 
pression and  general  appearance  gives  the  impression  of 
premature  aging,  the  eyelids  swell  and  bag.  There  is  an 
edema  of  the  extremities  which  does  not  pit  on  pressure, 
there  is  also  a  thickening  of  the  skin  in  the  gluteal  region, 
while  in  the  supraclavicular  region  there  are  swellings 
which  resemble  lipomata;  the  mucous  membranes  are 
thickened,  the  tongue  and  gums  swollen,  so  that  the  pa- 
tient speaks  slowly  and  with  difficulty. 

The  blood  changes  consist  in  reduction  of  the  red  cor- 
puscles, which  may  fall  as  low  as  2,000,000.  There  is  also 
said  to  be  a  leucocytosis.  The  patient  suffers  from  cold, 
complaining  of  feeling  chilly  even  in  warm  rooms. 

Should  the  operation  have  been  performed  in  youth  the 
patient  ceases  to  grow  in  height;  the  growth  in  breadth 
increasing  out  of  proportion,  the  genitalia  cease  to  de- 
velop. The  cause  of  the  arrest  of  growth  appears  to  be 
the  arrest  of  the  development  of  the  long  bones.  In  cases 
where  the  patient  has  lived  into  manhood,  the  epiphyses 
were  found  unaltered  and  the  ends  of  the  bones  not 
ossified.  The  symptoms  vary  in  degree  from  complete 
myxedema  to  slight  symptoms  which  may  be  difficult  to 
recognize. 

The  treatment  of  tetany  and  cachexia  strumipriva  con- 
sists in  the  administration  of  thyroid  gland  and  in  the 
former  condition  it  seems  probable  that  the  addition  of 
parathyroid  gland  would  be  of  service. 

Wounds  of  the  thyroid  seldom  occur.  Occasionally  in 
cases  of  suicide,  attempted  murder,  or  during  the  opera- 
tion for  tracheotomy  the  gland  may  be  wounded.     In  the 


120  THE    THYROID    AND    PARATHYROID    GLAND3- 

two  former  cases  there  is,  besides  the  wounding  of  the 
gland,  damage  to  the  vessels,  nerves  and  possibly  trachea, 
at  the  same  time. 

The  danger  in  these  wounds  of  the  thyroid  is  the  hem- 
orrhage, which  may  be  very  severe;  if  the  trachea  has 
been  cut  or  the  operation  of  tracheotomy  performed,  as- 
phyxia may  occur  by  the  blood  flowing  into  the  trachea. 
Should  the  gland  have  been  wounded  there  may  follow  a 
progressive  cirrhotic  condition,  which  may  progress  to  a 
more  or  less  pronounced  myxedema.         ' 

In  a  case  seen  by  the  writer,  a  suicide  in  cutting  across 
the  trachea,  wounded  the  thyroid  slightly ;  on  his  recovery 
from  the  wound  a  band  of  scar  tissue  contracted  the  tra- 
chea, pressing  on  the  gland,  causing  severe  dyspnea.  He 
was  operated  upon  and  the  dyspnea  ameliorated,  the  mel- 
ancholia disappeared  later  and  he  was  discharged.  About 
six  months  after  he  returned  to  the  hospital  showing  many 
of  the  symptoms  of  myxedema,  yet  suffering  from  acute 
mania.  He  was  put  upon  thyroid  treatment,  making  a 
very  rapid  and  complete  recovery. 


CHAPTER    VII. 

THE    THYROID    IN    INFECTIOUS    DISEASES. 

The  thyroid  gland  is  subject  to  congestion  under  the 
normal  conditions  of  puberty,  menstruation  and  preg- 
nancy; at  times  the  congestion  becomes  so  severe  as  to 
produce  dyspnea  and  asphyxia.  This  is,  however,  very 
rare.  The  patient  notices  a  marked  bilateral  enlargement 
of  the  neck,  usually  accompanied  with  mental  depression, 
an  increased  pulse  rate  and  slight  tremors.  If  the  condi- 
tion occurs  at  any  of  the  above  periods  it  will  completely 
disappear  in  a  few  days  of  its  own  accord,  or  there  may 
remain  a  slight  permanent  enlargement,  which  will  in- 
crease at  every  succeeding  period,  progressing  to  a  chronic 
goitre,  often  ending  in  degeneration  of  the  gland  and  con- 
sequent myxedematous  symptoms. 

Should  treatment  be  deemed  necessary  iodid  of  potas- 
sium or  Lugol's  solution  in  full  doses  will  usually  reduce 
the  tumor  in  a  few  weeks.  If  there  is  danger  of  asphyxia 
partial  excision  of  the  gland  should  be  resorted  to  in  pref- 
erence to  tracheotomy. 

In  the  acute  infectious  diseases  the  thyroid  gland  often 
suffers  more  or  less  severely  and  many  cases  of  cretinism, 
infantilism  and  myxedema  date  from  an  acute  infection. 

The  pathological  anatomy  in  these  cases  has  been 
studied  by  Eoger,  who  has  found  that  in  spite  of  the 
diversity  of  the  diseases,  which  include  scarlet  fever, 
diphtheria,  typhoid  fever,  cerebrospinal  meningitis, 
measles,  smallpox  and  purulent  peritonitis,  there  are  a 
number  of  characteristics  common  to  all. 

To  the  naked  eye  the  gland  appears  to  be  normal,  but 
is  increased  both  in  size  and  weight.     Taking  the  average 

121 


122 


THE    THYROID    AND    PARATHYROID    GLANDS. 


weight  of  the  normal  adult  gland  as  25  grins.,  he  has 
found  the  weight  above  30  grins.,  and  as  high  as  71  grms. 
In  these  hypertrophied  glands  the  microscopic  changes 
are  marked. 

The  color  of  the  gland  is  altered  from  the  normal  yel- 
lowish tint  to  a  red  or  violet  shade,  the  parenchyma  is 
uniformly  red  or  brownish,  marbled  with  violet.  A  part 
of  the  gland,  however,  may  retain  its  normal  color,  it  be- 
ing not  uncommon  to  find  one  lobe  congested  and  changed 
in  color  while  the  other  may  be  perfectly  normal  and  even 

the  affected  lobe  may  not 
be  uniformly  altered,  the 
base  being  the  portion  most 
often  affected. 

The  histological  lesions 
are  of  considerable  inter- 
est. The  connective  tissue 
is  in  general  but  little  al- 
tered ;  sometimes,  especial- 
ly in  infants,  it  contains  an 
excess  of  nuclei,  but  never, 
either  in  the  child  or  in 
adults,  are  the  masses  of 
leucocytes  observed  which 
are  seen  in  the  liver  and 
other  organs  in  infectious 
disease.  On  the  first  glance 
the  impression  is  given  that 
there  is  a  marked  increase 
in  connective  tissue,  which  is  due  to  the  presence  of  the  col- 
loid substance  within  the  vessels.  It  appears  as  if  thick 
intravascular  bands  converged  towards  the  vessels,  but 
these  bands  are  not  formed  from  connective  tissue.  With 
a  higher  power  it  is  seen  that  the  fibres  are  eccentric  and 
that  the  intermediate  spaces  are  filled  with  a  homogene- 


Fig.  32.— Congestion  of  the  thyroid. 


THE    THYEOID    IN    INFECTIOUS    DISEASES.  123 

ous  substance,  uniformly  colored,  giving  the  reactions  of 
colloid  substance  dilating  the  lymphatic  spaces.  The 
whole  appears  like  a  network  surrounding  the  vesicles. 
This  condition  exists  in  nearly  every  thyroid  gland  in  in- 
fectious disease. 

The  alterations  in  the  vessels  are  less  acute,  they  are 
dilated  and  filled  with  red  corpuscles,  as  are  the  capil- 
laries. In  a  case  of  smallpox  the  red  corpuscles  had 
extravasated,  mixing  with  the  leucocytes  and  colloid, 
forming  a  magma  without  definite  limit  in  the  midst  of 
which  true  thyroid  cells  could  be  distinguished,  the  hem- 
orrhage had  remained  interstitial.  In  a  case  of  diphtheria 
the  blood  had  penetrated  into  the  interior  of  the  vesicles, 
but  the  lesion  was  limited  and  affected  only  a  small  por- 
tion of  the  parenchyma.  Arteritis  and  phlebitis  occur, 
the  intima  thickens,  progressing  into  the  interior  of  the 
vessel,  producing  thrombosis  with  more  or  less  complete 
obstruction  of  the  lumen.  Periarteritis  and  periphlebitis 
are  rare.  The  most  interesting  lesions  are  those  of  the 
parenchyma,  the  vesicles  being  altered  in  form,  dimension 
and  constitution,  the  colloid  being  sometimes  altered  in  its 
essential  qualities.  Usually  the  vesicles  are  reduced  in 
size,  as  the  intravascular  vessels  are  diluted  by  colloid, 
several  of  the  acini  may  no  longer  contain  colloid  and 
their  centre  is  occupied  by  cells  in  a  state  of  disintegra- 
tion. The  connective  tissue  surrounding  the  vesicle  is 
easily  made  out,  but  the  lining  cells  have  desquamated 
from  the  walls  in  many  places,  and  are  in  the  centre  of  the 
vesicle  mixed  with  the  colloid.  The  protoplasm  of  these 
cells  is  granular,  the  nucleus  large,  of  irregular  shape, 
staining  badly  with  hematoxylin.  Sometimes  several  cells 
are  massed  together  in  the  centre  of  the  vesicle,  in  the 
midst  of  which  are  the  nuclei  in  degeneration.  Other 
vesicles  on  the  contrary  contain  a  certain  amount  of  nor- 
mal colloid. 


124  THE    THYROID    AND    PAEATHYEOID    GLANDS. 

The  colloid  substance  does  not  react  to  the  stains  as 
normally.  Safranin  instead  of  giving  it  a  strong  red  only 
produces  a  faint  rose  color;  sometimes  it  loses  its  affinity 
for  eosin  and  remains  yellow,  to  aurantium  it  fails  to  react 
normally,  producing  a  dirty  brown,  very  different  from  the 
characteristic  light  yellow.  Occasionally  certain  vesicles, 
containing  instead  of  colloid  a  mass  of  brownish  granula- 
tions, fail  to  take  eosin,  but  become  green  with  thionin. 
Sometimes  these  granulations  fill  a  whole  vesicle  or. there 
may  be  only  a  small  mass  among  the  desquamated  cells. 
They  only  exist  among  the  glands,  which  are  much  altered. 

When  the  lesions  produced  in  the  thyroid  by  the  infec- 
tious diseases  are  very  marked,  the  secretion  of  colloid 
either  ceases  or  is  replaced  by  granulations  of  abnormal 
reaction.  The  vesicles  are  uniformly  filled  with  desqua- 
mated cells  crowded  together,  which  have  large,  clear  pro- 
toplasm more  rarely  granulated.  The  walls  of  the  ves- 
icles have  degenerated  and  are  no  longer  able  to  contain 
the  colloid  substance. 

The  pathology  of  the  parathyroids  in  infectious  diseases 
has  so  far  received  but  little  attention.  Roger  examined 
them  in  one  case  of  scarlet  fever  and  in  a  case  of  diph- 
theria. In  the  case  of  a  woman  dying  of  scarlet  fever, 
where  the  changes  in  the  thyroid  were  comparatively 
slight,  the  four  parathyroids  showed  marked  lesions.  The 
spaces  in  the  connective  tissue  instead  of  being  exactly 
filled  with  epithelium,  as  in  normal  glands,  were  half 
empty.  The  cells  were  not  dispersed  regularly  on  the 
base  membrane,  and  were  massed  in  the  centre  of  the 
spaces.  They  consisted  of  granular  protoplasm  with  ill- 
defined  limits.  The  nucleus  stained  well.  These  lesions 
were  found  in  various  parts  of  the  gland;  at  the  same 
time  there  was  much  healthy  tissue.  In  the  case  of  diph- 
theria they  found  the  same  lesions. 

The  above  are  the  lesions  found  to  a  greater  or  less 


THE    THYROID    IN    INFECTIOUS   DISEASES.  125 

extent  in  all  infectious  diseases ;  there  are,  however,  some 
variations  distinctive  of  the  different  infections. 

In  scarlet  fever  the  gland  suffers  very  severely.  In  15 
cases  examined  by  Roger  only  two  were  found  to  be  about 
normal,  one  being  that  of  a  child  of  16  months,  the  other 
in  a  woman  of  30,  but  in  the  latter  the  parathyroids  were 
markedly  abnormal.  Congestion  was  always  present; 
there  was  no  hemorrhage.  The  walls  of  the  vessels  were 
affected.  In  two  cases  endarteritis  thrombus  was  ob- 
served. Hypersecretion  of  the  colloid  was  observed  in 
nearly  every  case,  twice  the  colloid  was  altered,  reacting 
abnormally  to  the  staining  reagents. 

In  measles  the  gland  resists  the  disease  better  than  in 
scarlet  fever.  In  only  half  of  the  glands  examined  was 
there  any  abnormality  observed. 

In  smallpox,  in  the  gland  of  the  one  case  examined,  the 
lesions  were  very  severe.  The  gland  was  hypertrophied 
and  much  congested.  This  case  differed  from  scarlet 
fever  in  the  presence  of  small  parenchymatous  hemor- 
rhages, at  the  same  time  the  colloid  was  abnormal,  being 
brown  and  granular. 

In  diphtheria  the  hypersecretion  is  less  marked  than  in 
scarlet  fever,  the  vesicles  contain  numbers  of  desquamated 
cells  and  colloid  substance  is  usually  altered;  rarely  is 
there  any  hemorrhage. 

The  intensity  of  the  lesions  does  not  appear  to  depend 
on  the  duration  of  the  disease  nor  is  it  affected  by  inter- 
current diseases.  Out  of  the  15  cases  examined,  four  suc- 
cumbed to  streptococcus  complications,  but  showed  no 
complication  of  the  lesions. 

In  measles  it  is  somewhat  difficult  to  say  what  are  the 
lesions  of  the  gland  in  an  uncomplicated  case,  as  death 
from  measles  is  rare,  the  complications  usually  being 
bronchopneumonia,  rarely  meningitis,  gangrene  of  the 
pharynx  and  purulent  coryza. 


126  THE    THYROID    AND    PARATHYROID    GLANDS. 

Gamier  made  some  experiments  on  animals,  inoculating 
them  either  under  the  skin  or  in  the  veins,  and  others  in 
the  thyroid  arteries ;  under  the  latter  condition  the  results 
were  very  instructive.  He  used  the  staphylococcus 
aureus,  which  produced  a  diffuse  thyroiditis;  if  the  cul- 
tures were  very  virulent  they  produced  parenchymatous 
lesions;  if  attenuated,  interstitial  lesions.  In  the  first 
case  the  vesicles  were  reduced  in  size,  they  contained  pale 
colloid,  the  epithelial  cells  were  swollen,  their  protoplasm 
staining  uniformly,  and  in  places  they  appeared  as  fused 
together  in  a  mass,  the  nucleus  was  swollen,  staining  badly, 
the  vessels  gorged  with  blood,  the  connective  tissue  appar- 
ently normal.  If  the  culture  used  was  extremely  virulent 
there  were  destructive  lesions ;  with  death  of  the  cells  the 
vesicle  disrupted,  the  colloid  filling  the  lymph  spaces. 

If  an  attenuated  culture  was  injected  there  was  arteritis ; 
in  the  vesicles  were  masses  of  leucocytes,  in  the  centre  of 
which  were  degenerated  epithelial  cells. 

The  experiments  with  the  typhoid  bacillus  produced  the 
same  diverse  anatomical  lesions,  but  more  diffuse.  With 
very  virulent  cultures  hemorrhagic  thyroiditis  occurred. 
With  less  virulent  cultures  there  was  epithelial  degenera- 
tion, capillary  congestion  and  endarteritis.  When  the 
animals  were  allowed  to  survive  sclerosis  occurred  in  the 
form  of  bands  of  connective  tissue,  which  divided  the 
gland  into  segments.  The  vesicles  appeared  to  be  normal, 
but  their  walls  were  much  thickened.  There  was  also  a 
certain  quantity  of  endarteritis  and  periarteritis. 

Toni  experimented  on  the  same  lines  with  the  pneumo- 
coccus,  the  typhoid  bacillus  and  anthrax.  He  used  less 
virulent  cultures  than  Gamier  and  therefore  did  not  ob- 
tain such  marked  results,  but  the  same  in  kind.  These 
experiments  show  that  the  infectious  diseases  produce 
certain  lesions  in  the  gland  which  vary  according  to  the 
intensity  of  the  infection. 


THE    THYBOID    IN    INFECTIOUS   DISEASES.  127 

Suppurative  thyroiditis  is  uot  uncommon  in  the  infec- 
tious diseases,  and  hemorrhagic  thyroiditis  is  rare,  occur- 
ring most  often  in  smallpox.  Sclerosis  of  the  thyroid 
may  occur  as  the  result  of  any  of  the  acute  infectious  dis- 
eases, and  also  in  tuberculosis  and  syphilis,  which  accounts 
for  the  numerous  cases  of  myxedema  and  infantilism 
which  occur  after  a  severe  illness.  The  symptoms  of 
myxedema  may  not  occur  for  months  or  years  after  the 
disease,  the  sclerosis  progressing  slowly. 

When  the  inoculations  were  made  at  a  distance  from 
the  gland,  there  were  but  slight  pathological  changes  in 
the  glands.  The  staphylococcus,  the  typhoid  bacillus  and 
anthrax  produced  no  lesion  that  could  be  detected,  the 
streptococcus,  however,  produced  lesions  resembling  those 
described  as  occurring  in  man. 

By  injection  of  diphtheritic  toxin  into  a  guinea  pig 
Eoger  observed  lesions  in  the  gland  resembling  those  oc- 
curring in  man.  The  colloid  substance  leaves  the  alveoli, 
entering  the  lymphatics ;  at  times  it  is  so  abundant  as  to 
entirely  mask  the  vesicles,  and  in  the  lakes  that  form  there 
are  epithelial  cells.  At  other  points  the  cells  desquamate 
into  the  middle  of  the  vesicles.  All  the  colloid  passes  into 
the  vessels  but  preserves  its  normal  characteristics. 

The  tetanus  toxin  produced  rather  different  results,  the 
lesions  were  less  marked  and  consisted  principally  in  a 
slight  hypersecretion.  In  one  case  which  developed  slow- 
ly the  colloid  was  granular  and  yellow,  taking  the  stain 
poorly. 

The  effect  of  the  inoculations  of  cultures  and  of  toxins 
upon  the  gland  seems  to  resemble  very  much  the  action 
of  nitrate  of  pilocarpin  and  iodid  in  producing  a  hyper- 
secretion which  flows  into  and  gorges  the  lymphatics, 
dilating  the  vesicles,  and  there  appears  but  one  vast  mass 
of  colloid  scattered  irregularly,  among  which  are  rows  of 
nuclei,  the  cells  having  desquamated  and  filled  the  cavity 


128  THE    THYROID    AND    PARATHYROID    GLANDS. 

of  the  vesicles,  their  nuclei  staining  badly,  showing  ir- 
regular outlines,  the  colloid  remains  normal,  while  in  the 
infectious  diseases,  although  the  anatomical  lesions  are  the 
same,  the  colloid  is  evidently  chemically  changed,  so  that 
while  there  is  a  hypersecretion  there  may  also  be  "dys- 
thyroidation "  which  may  amount  to  a  suppression  of 
function  of  the  gland. 

It  follows,  therefore,  that  during  the  course  of  infectious 
diseases  there  are  secretory  troubles  in  the  thyroid  gland 
as  well  as  in  the  other  glands  of  the  body,  a  period  of 
superactivity  followed  by  a  diminution  or  alteration  of 
function,  as  the  liver  secretes  abnormal  pigments  so  the 
thyroid  secretes  abnormal  colloid  substance. 

Usually  the  lesions  are  slight  and  are  quickly  repaired, 
but  it  may  not  always  be  so,  pathological  conditions  may 
continue  to  exist  and  may  be  progressive,  producing  par- 
tial or  complete  loss  of  function,  accompanied  with  the 
symptoms  of  hypo-  and  athyroidea. 


CHAPTER    VIII. 

ACUTE    THYROIDITIS. 

Acute  inflammations  of  the  thyroid  were  observed  in 
the  middle  of  the  seventeenth  century,  terminating  as  sup- 
purative goitres.  Libert  in  1862  and  Bauchet  in  1877 
wrote  monographs  on  the  subject  which  are  classical  in 
France. 

Acute  thyroiditis  is  always  due  to  infection,  a  predis- 
posing cause  being  a  goitrous  condition  of  the  gland  which 
then  becomes  cystic.  The  disease  occurs  most  frequently 
in  women,  usually  between  the  ages  of  20  and  40,  occa- 
sionally in  children,  and  very  rarely  over  50  years  of  age. 

Among  the  causes  of  susceptibility  besides  goitre  are 
trauma  and  cold.  The  trauma  may  be  due  to  pressure, 
such  as  strangulation.  When  the  inflammation  is  pre- 
ceded or  accompanied  by  a  cold  it  is  due  to  an  infection, 
usually  streptococci  from  a  pharyngitis.  The  gland  is 
liable  to  infection  from  its  circulation,  a  venous  conges- 
tion being  easily  produced  by  shouting  or  long  talking, 
during  labor,  and  in  various  other  ways ;  it  also  may  occur 
at  the  climacteric.  Nearly  always,  if  not  always,  thy- 
roiditis is  a  secondary  lesion  during  the  course  of  an  in- 
fectious disease,  among  the  most  common  being  typhoid 
fever.  The  pus  in  the  gland  has  been  found  to  contain 
the  bacillus  of  Eberth  by  Tavel,  Kocher  and  many  others,, 
either  in  pure  culture  or  associated  with  other  organisms. 
Some  cases  can  be  attributed  to  a  secondary  pyemia,  it 
having  been  observed  in  purulent  infections,  posttrau- 
matic, postoperative  or  other  suppurative  lesions.  It  is,, 
however,  in  puerperal  infection  that  the  disease  is  most 
common,  the  organism  being  usually  a  streptococcus. 

9  129 


130  THE    THYROID    AND    PAEATHYEOID    GLANDS. 

The  diseases  which  may  produce  acute  thyroiditis  are 
the  eruptive  fevers,  scarlet  fever,  measles,  smallpox,  ery- 
sipelas, diphtheria,  influenza,  pneumonia,  articular  rheu- 
matism, and  particularly  malaria.  It  has  also  been  ob- 
served to  accompany  or  follow  bronchitis,  pharyngitis  and 
coryza.  In  diseases  of  the  digestive  tract  it  has  been  ob- 
served in  catarrh  of  the  stomach  when  the  bacillus  strep- 
tococcus lanceolatus  was  isolated,  in  acute  enteritis,  and 
in  proctitis  when  the  bacillus  coli  communis  was  found. 
The  staphylococcus  pyogenes  was  found  in  a  gland  during 
a  case  of  osteomyelitis. 

The  symptoms  vary  with  the  accompanying  disease. 
Should  there  be  a  primary  infection  of  the  gland  there 
would  be  the  chills,  fever,  malaise  and  headache  common 
to  all  infections,  followed  by  the  more  distinctive  symp- 
toms of  pain  felt  in  the  region  of  the  gland,  which  is  in- 
creased on  pressure,  localized  in  the  majority  of  cases  in 
one  lobe,  usually  the  right;  the  pain  increases  on  move- 
ment, especially  in  extension,  causing  the  patient  to  carry 
his  head  thrust  forward  and  bent  downward  so  as  to  relax 
the  muscles  as  much  as  possible;  sometimes  supporting 
the  chin  with  the  hand ;  often  the  pain  radiates  to  the  ears 
and  neck.  At  the  end  of  the  first  or  second  day  the  en- 
larged lobe  usually  becomes  palpable,  very  rarely  the 
tumor  is  confined  to  the  isthmus. 

On  palpation  the  tumor  is  found  to  be  attached  to  the 
deep  tissues  moving  up  and  down  on  deglutition,  it  feels 
;at  first  hard  and  perhaps  elastic;  there  may  be  displace- 
ment of  the  trachea,  which  becomes  compressed  should 
the  tumor  reach  a  large  size,  causing  dyspnea,  which  may 
require  prompt  surgical  interference. 

The  compression  of  the  vessels  causes  distention  of  the 
superficial  veins,  headache,  singing  in  the  ears,  vertigo, 
and  sometimes  epistaxis.  Pressure  on  the  pneumogastric 
nerve  may  also  add  to  the  dyspnea.     The  patient  is  an- 


ACUTE    THYKOIDITIS.  131 

noyed  by  a  dry  cough,  accompanied  by  a  slight  expectora- 
tion streaked  with  blood,  or  there  may  be  true  hemoptysis. 
The  voice  is  rough,  harsh  and  thick,  speech  slow  and  diffi- 
cult, sometimes  the  aphonia  is  absolute.  The  respiration 
becomes  painful  and  wheezy.  There  may  be  pressure  on 
the  esophagus,  or  pressure  on  the  nerves,  producing  pain- 
ful and  difficult  deglutition,  with  a  feeling  as  if  there  were 
a  foreign  body  at  the  back  of  the  throat ;  vomiting  may  be 
very  severe. 

The  irritation  of  the  various  nerves  compressed  by  the 
goitre  may  cause  a  number  of  very  varied  symptoms,  such 
as  pains  in  various  regions  of  the  body,  formications  and 
paralysis  of  the  hands.  This  latter  symptom  is  said  to  be 
occasionally  produced  by  a  functional  trouble  of  the  gland. 

Thyroiditis  may  terminate  by  resolution,  by  suppura- 
tion or  by  gangrene.  In  the  first  case  the  symptoms  in- 
crease for  three  or  four  days,  then  remain  stationary  for 
some  days,  characterized  by  fever  with  matutinal  remis- 
sions with  a  more  or  less  serious  condition  for  five  or  six 
days.  At  the  end  of  this  time  the  gland,  which  has  been 
steadily  growing,  commences  to  diminish  in  volume,  the 
tumor  disappearing  in  about  twenty  days.  Sometimes 
there  is  a  return  of  the  swelling  after  a  few  days.  In 
many  cases  the  gland  never  returns  to  its  former  volume, 
remaining  permanently  enlarged. 

Suppuration  occurs  in  about  60  to  70  per  cent  of  the 
cases,  as  in  all  cases  of  infection  there  are  chills,  fever, 
malaise,  headache,  etc.,  but  there  is  also  a  change  in  the 
character  of  the  pain,  which  becomes  lancinating ;  the  skin 
over  the  gland,  which  has  up  to  this  time  remained  normal 
or  slightly  streaked  with  the  engorged  veins,  becomes  hot 
and  red,  losing  its  mobility  over  the  deeper  tissues.  The 
cervical  region  becomes  enlarged,  accompanied  by  an 
edema  in  the  substernal  region  as  well  as  in  the  upper 
portion  of  the  thorax. 


132  THE    THYROID   AND    PAEATHYKOID    GLANDS. 

Fluctuation  is  always  late  in  appearing  and  is  difficult 
to  detect,  owing  to  the  depth  of  the  tumor,  and  is  not  of 
such  symptomatic  value  as  the  discolorations  and  edema 
of  the  neck.  Exploration  by  puncture  will  usually  have 
to  be  resorted  to  if  it  is  necessary  to  operate  early  in  the 
disease.  As  the  pus  is  very  thick  and  the  tumor  perhaps 
a  long  distance  from  the  surface,  even  a  negative  result 
cannot  be  relied  on. 

If  the  abscess  is  left  alone  it  usually  opens  externally ; 
the  skin  becomes  red  and  taut  before  perforation,  the  pus 
is  either  a  serous  liquid,  fetid,  bloody  or  contains  gas. 
Usually  cicatrization  is  rapid,  at  others  a  fistula  may  re- 
main for  a  month  or  even  years.  The  abscess  may  per- 
forate into  the  larynx,  trachea  and  esophagus,  or  into  the 
surrounding  tissue;  in  the  latter  case  the  condition  be- 
comes very  grave,  sinus  forming  in  the  direction  of  the 
face,  the  neck,  the  clavicles  or  the  pleura. 

Gangrenous  thyroiditis  is  rare,  there  being  only  eight 
cases  on  record  and  is  of  very  grave  prognosis.  The  con- 
dition develops  rapidly,  the  gas  forming  under  the  skin 
causes  distention  which  rapidly  breaks  down,  leaving  a 
large  opening  in  which  the  carotid  arteries  and  the  arch 
of  the  aorta  may  be  visible. 

A  rheumatismal  thyroiditis  occurs  during  an  acute  at- 
tack of  rheumatism,  never  suppurates,  and  is  character- 
ized by  a  mobile  and  fugitive  congestion,  often  developing 
with  great  rapidity  within  a  few  hours  and  disappearing 
in  the  same  manner.  The  pain  in  the  region  of  the  gland 
is  very  intense,  causing  the  patient  to  thrust  his  head  for- 
ward to  support  his  chin  with  his  hand.  It  rarely  lasts 
more  than  three  or  four  days,  though  it  may  return  or 
alternate  with  other  manifestations ;  the  neck  may  remain 
permanently  enlarged. 

The  thyroiditis  of  mumps  is  somewhat  similar  in  its 
character  to  that  of  rheumatism,  but  is  extremely  rare  and 
has  not  been  observed  to  suppurate. 


ACUTE    THYKOIDITIS.  133 

The  thyroiditis  of  grippe  may  attain  the  size  of  a  hen's 
egg,  it  recedes  about  the  sixth  day  and  does  not  suppurate. 
The  symptoms  which  it  produces  are  those  of  hyperthy- 
roidea,  viz :  vertigo,  palpitations,  tachycardia,  tremors,  etc. 

The  thyroiditis  of  malaria  rarely  suppurates,  except  in 
goitrous  cases. 

The  thyroiditis  of  typhoid  is  the  most  frequent  form  of 
secondary  acute  thyroiditis,  usually  appearing  at  the  com- 
mencement of  convalescence,  and  is  probably  a  local  in- 
fection from  the  bacillus  of  the  disease.  When  it  occurs 
during  convalescence  there  is  a  rise  in  temperature  with  a 
hyperleucocytosis  instead  of  the  hypoleucocytosis  of  the 
typhoid  fever.  Suppuration  is  frequent,  occurring  in 
about  50  per  cent.  Generally  the  course  is  favorable  with 
rapid  cure. 

Pyemic  thyroiditis  is  a  much  more  grave  disease  than 
the  other  forms,  as  the  points  of  infection  are  scattered 
through  the  gland,  rendering  the  probabilities  of  a  favor- 
able termination  very  remote. 

The  pathological  anatomy  of  this  condition  requires 
only  a  short  description.  In  non- suppurative  conditions 
the  tissue  is  much  congested,  of  a  dark  red  color,  dotted 
with  small  hemorrhages.  Under  the  microscope  pigment 
degeneration  of  the  cells  is  found,  congestion  of  the  capil- 
laries and  the  colloid  infiltrated  into  the  interstitial  tissue. 

The  suppuration  is  generally  in  the  bands  of  connective 
tissue,  looking  under  the  microscope  like  small  miliary 
abscesses. 

The  diagnosis  of  acute  thyroiditis  presents  but  little 
difficulty.  The  treatment  depends  upon  the  cause,  it 
being  directed  to  the  general  infection.  A  purgative  to 
deplete  the  system  has  often  a  good  effect  in  reducing  the 
tumor,  external  application  of  belladonna  ointment  or  of 
hot  compresses  may  be  of  service.  If  there  is  suppura- 
tion the  abscess  should  be  opened  as  soon  as  it  can  be 
definitely  defined,  usually  it  will  heal  up  rapidly. 


134  THE    THYROID    AND    PARATHYROID    GLANDS. 

TUBERCULOSIS    OE    THE    THYROID    GLAND. 

The  thyroid  gland  is  subject  to  two  kinds  of  lesions  in 
tuberculosis;  it  may  be  invaded  by  the  tubercle  bacilli 
with  the  development  of  the  typical  granulations,  or  the 
toxins  formed  in  the  general  system  may  produce  sclerosis 
and  consequent  loss  of  function.  Tubercle  formation  in 
the  gland  is  rare,  on  the  contrary  the  sclerosis  of  the  gland 
is  always  present. 

Previous  to  Lebert's  work  in  1862  the  pathological  re- 
search on  the  thyroid  had  been  principally  confined  to 
goitre.  The  latter  investigated  and  found  miliary  tu- 
bercles in  the  gland  of  a  woman  25  years  of  age.  Vir- 
chow  reported  a  case  of  caseous  tubercle,  which  was  fol- 
lowed shortly  after  by  reports  of  cases  by  Fraenkel,  Bruns, 
Rolleston  and  others.  Chiari  found  tubercles  in  the  thy- 
roid in  4  per  cent  of  his  cases.  Weigert  found  tubercles 
in  the  thyroid  of  all  of  the  eleven  cases  of  miliary  tubercu- 
losis that  he  examined;  others  have  not  found  them  so 
frequently.  They  are  more  common  in  young  persons  and 
children  than  in  older  patients. 

In  certain  tubercular  patients  the  tubercles  produced 
by  the  disease  cause  a  swelling  of  the  gland,  which  may  be 
so  great  as  to  cause  discomfort  to  the  patient,  occasionally 
compressing  the  neighboring  organs,  producing  the  vari- 
ous symptoms  already  described.  Fumolard  describes  a 
form  of  this  infection  under  the  title  of  follicular  thyroid- 
itis, being  subacute  in  its  progress,  characterized  by  suc- 
cessive infections,  producing  fistulous  openings. 

In  the  second  form  the  gland  contains  caseous  nodules, 
but  is  not  so  enlarged  as  to  press  on  the  neighboring  or- 
gans. In  Virchow's  case  the  nodule  was  about  the  size  of 
a  cherry.  In  a  case  of  Grasset  and  Estor's  the  left  lobe 
was  double  the  normal  size,  hard,  covered  with  small 
tumors,  the  size  of  a  lentil,  on  the  anterior  and  superior 
surface,  attached  to  the  gland  by  a  pedicle.     Rolleston  re- 


TUBEECULOSIS    OF    THE    THYROID    GLAND. 


135 


ported  a  case  where  there  was  a  caseous  mass  in  the  gland 
with  an  abscess  having  two  orifices  opening  into  the 
esophagus,  one  the  size  of  a  ten-cent  piece,  the  other  much 
smaller. 

The  third  form  corresponds  to  miliary  tuberculosis,  the 
tuberculous  granulations  are  distributed  on  the  surface 
and  in  the  parenchyma  of  the  gland,  the  granulations  are 
yellow  and  easily  distinguished  with  the  naked  eye  and  of 
about  the  size  of  a  millet  seed.  Sometimes  the  granula- 
tions are  very  small  and  can  only  be  recognized  by  the  aid 
of  the  microscope,  the  gland  appearing  normal  on  macro- 
scopical  examination  and  is  not  increased  in  volume. 

In  the  neighborhood  of  the 
tubercle  the  gland  is  pro- 
foundly altered,  the  position 
of  the  vesicles  is  indicated 
by  the  granular  cells,  which 
are  in  circular  or  elliptical 
groups,  but  poorly  stained. 
The  cavity  of  the  vesicles 
does  not  contain  colloid  but  a 
few  fibrils  surrounding  the 
epithelial  cells.  Between  the 
vesicles  there  is  an  increase 
of  fibrous  tissue,  enclosing 
numbers  of  fixed  proliferated  cells. 

On  injecting  cultures  of  the  tubercle  bacilli  into  the 
thyroid  gland  of  animals  by  way  of  the  thyroid  artery 
granulations  were  produced  of  the  same  type  as  those 
found  in  man.  The  first  effect  of  the  bacillus  or  its  toxin 
is  to  cause  degeneration  of  the  cells.  As  the  most  highly 
differentiated  elements  are  always  least  resistant,  the  ves- 
icular epithelium  was  the  first  attacked.  If  the  cultures 
were  very  virulent  or  a  large  quantity  was  injected,  and 
the  organism  like  that  of  the  guinea  pig  very  susceptible, 


Fig.  33. ^Tuberculosis  of 
Thyroid. 


136  THE    THYEOID    AND    PAEATHYROID    GLANDS. 

this  reaction  is  not  marked.  If  the  action  is  less  energetic 
or  the  resistance  greater  the  reaction  occurs.  As  soon  as 
infection  has  become  general,  the  toxins  formed  in  the 
other  parts  of  the  body  are  brought  to  the  gland  by  the 
circulation  and  sclerotic  lesions  commence.  If,  on  the 
other  hand,  the  bacilli  penetrate  and  find  a  nidus  in  the 
gland  the  quantity  of  toxin  formed  produces  a  more  in- 
tense reaction  and  tubercular  granulations. 

Sclerosis  of  the  thyroid  is  almost  invariably  found  in 
tuberculous  disease  and  has  been  described  by  Gamier  as 
occurring  in  eleven  out  of  twelve  cases  examined.  Char- 
rin  and  Nathan  Lerrier  showed  that  it  exists  in  the  newly- 
born  of  tuberculous  mothers.  In  a  case  described  by 
Roger,  where  the  gland  was  not  sclerotic,  the  gland 
weighed  90  grins.,  being  three  times  larger  than  normal, 
containing  neither  granulations  nor  sclerosis ;  the  vesicles 
were  filled  with  colloid  and  the  cells  apparently  normal. 
It  would  appear  that  the  existence  of  a  goitre  had  tended 
to  preserve  the  gland  from  the  action  of  the  toxin. 

It  is  difficult  to  determine  what  symptoms  in  phthisis, 
if  any,  are  due  to  sclerosis  of  the  thyroid.  The  tachycar- 
dia, so  often  noticed  in  the  early  stages  of  tuberculosis, 
may  be  produced  by  a  superactivity  preceding  the  destruc- 
tion of  the  tissue  and  sclerosis.  The  sclerosis  of  the  gland 
must  necessarily,  if  going  far  enough,  produce  loss  of 
function  of  the  gland  and  may  account  for  some  of  the 
many  varied  symptoms  which  occur  in  the  disease.  The 
fact  that  patients  who  recover  from  tuberculosis  often 
become  very  stout  may  be  due  to  a  hypothyroidea  pro- 
duced by  a  sclerotic  condition  of  the  gland. 

Gautier  and  Bourcet  have  shown  that  the  iodin  and  ar- 
senic disappear  from  the  gland  in  tuberculosis,  which  may 
account  for  the  troubles  of  the  skin  and  of  the  menstrual 
function  and  he  claims  to  have  removed  these  symptoms 


TUBERCULOSIS    OF    THE    THYROID    GLAND.  137 

by  the  administration  of  cacodylate  of  soda  combined  with 
very  small  quantities  of  iodin. 

A  macroscopic  examination  of  the  gland  shows  that  it  is 
much  reduced  in  size,  weighing  as  low  as  8  grins.,  the  sur- 
face is  paler  than  normal  on  section,  the  tissue  is  irregu- 
larly colored,  partly  yellow  and  partly  pink ;  the  gland  is 
harder  than  normal  and  in  advanced  cases  the  bands  of 
connective  tissue  can  be  distinctly  seen. 

The  microscopic  examination  shows  either  a  pure  scle- 
rosis or  the  latter  associated  with  parenchymatous  altera- 
tions. The  most  common  lesion  is  atrophic  sclerosis  while 
more  rarely  there  is  a  hypertrophic  sclerosis. 

In  trophic  sclerosis  the  connective  tissue  may  be  diffuse 
and  irregular,  at  other  times  regularly  distributed,  form- 
ing geometrical  figures  more  or  less  typical.  In  the  first 
case  the  tissue  is  abundant,  surrounding  the  vessels  in 
concentric  circles,  giving  the  idea  of  a  lobular  formation. 
The  vesicles  are  compressed  between  the  bands  and  may 
be  empty  of  colloid.  The  external  walls  of  the  arteries 
are  thickened,  often  accompanied  by  endarteritis,  the 
lumen  is  decreased  and  sometimes  obliterated.  In  the 
veins  the  lesions  are  usually  less  marked. 

The  parenchyma  is  little  changed,  the  vesicles  appear- 
ing normal,  but  in  certain  parts  the  gland  shows  a  condi- 
tion of  functional  hyperactivity.  The  islands  of  vesicles 
formed  by  the  bands  of  connective  tissue  secrete  actively, 
the  cellular  detritus  infiltrates  into  the  vesicles  while  occa- 
sionally the  colloid  appears  in  the  lymph  spaces.  Some- 
times the  sclerosis  is  accompanied  by  the  formation  of 
abnormal  colloid. 

In  hypertrophic  sclerosis  the  gland  is  enlarged  and  may 
weigh  as  much  as  52  grms.,  the  sclerosis  is  irregularly 
distributed,  and  in  the  neighborhood  of  the  larger  vessels 
are  large  islands  of  vesicles.  The  parenchyma  is  in  a 
state  of  active  cell  proliferation,  the  irritation  of  the  toxin 


138  THE    THYROID    AND    PARATHYROID    GLAXDS. 

has  evidently  produced  an  abnormal  multiplication  of  the 
elements,  the  cells  appearing  healthy  but  of  small  se- 
cretory power.  It  is  probable  that  this  hypertrophy  is 
the  first  effect  of  the  action  of  the  toxins  which  progresses 
to  atrophy  of  the  gland. 


CHAPTER    IX. 

SYPHILIS    OF    THE    THYROID. 

The  thyroid  gland  is  sometimes  the  seat  of  a  syphilitic 
inflammation  in  secondaries  or  tertiaries,  the  gland  be- 
coming so  large  as  to  cause  dyspnea,  but  this  is  excep- 
tional. Wolfler  records  a  case  where  the  thyroid  was 
found  to  contain  a  gumma  the  size  of  a  fist.  Fraenkel 
reports  a  case  which  died  of  syphilis  of  the  trachea,  lungs 
and  liver.  At  the  autopsy  it  was  found  that  between  the 
isthmus  and  the  right  lobe  there  was  a  mass  of  yellow 
substance  which,  on  microscopical  examination,  proved  to 
have  developed  in  the  interfollicular  tissue  and  had  com- 
pressed and  invaded  the  parenchyma  of  the  gland.  The 
lesion  is  differentiated  from  tubercle  by  the  absence  of 
giant  cells  and  degeneration. 

Hereditary  syphilis  is  occasionally  found  in  the  thyroid 
gland.  Demme  found  small  gummas  in  five  cases.  Fiirst 
records  a  case  of  a  child  born  of  a  syphilitic  mother  wlm 
presented  none  of  the  typical  symptoms  but  had  a  large 
goitre  which  he  considered  to  be  of  syphilitic  origin. 

Gamier  studied  the  glands  of  five  newly-born  syphilitic 
children.  In  only  one  case  was  the  gland  healthy.  The 
lesions  were  remarkable  as  being  diametrically  opposite 
to  those  found  in  the  adult;  the  colloid  substance  instead 
of  being  increased  was  reduced  or  absent.  The  vesicles 
were  uniformly  full  of  cells,  the  capillaries  dilated,  small 
hemorrhagic  points  scattered  through  the  gland  and  at 
the  same  time  focuses  of  cellular  degeneration.  These 
lesions  are  not  confined  to  hereditary  syphilis  but  occur 
more  or  less  marked  in  all  cases  of  infection  of  the  fetus. 
These  lesions  are  of  importance  as  they  may  account  for 

139 


140  THE    THYROID    AND    PARATHYROID    GLANDS. 

many  of  the  troubles  occurring  in  the  development  of  the 
child. 

Abraham  reports  three  cases  of  women  who  developed 
exophthalmic  goitre,  the  first  five  months  after  the  pri- 
mary lesion,  the  second  during  the  height  of  secondary 
infection,  and  the  third  two  years  after  infection,  all  of 
whom  were  cured  by  antisyphilitic  treatment. 

Faisans  and  Audistere  reported  a  case  with  both  gonor- 
rheal and  syphilitic  infection,  who  developed  a  pseudo- 
myxedema  in  which  the  myxedematous  symptoms  were 
not  affected  by  mercurial  treatment  but  disappeared 
under  thyroid  feeding. 

Kohler  has  reported  cases  of  myxedema  following 
syphilis,  and  Demme  has  observed  symptoms  of  Base- 
dow's disease  to  occur. 

CANCER   OF    THE   THYEOID. 

Cancer  of  the  thyroid  gland  is  rare,  occurring  only  19 
times  in  10,000  cases  and  very  rarely  except  in  glands 
which  are  goitrous.  It  usually  appears  between  the  for- 
tieth and  fiftieth  year.  Schuh  observed  it  in  a  young  man 
of  16,  and  Demme  in  a  child.  Traumatism  is  probably  a 
factor  and  Kauffman  suggests  pregnancy  as  favoring  its 
development,  owing  to  the  congestion  of  the  gland  during 
that  period. 

Usually  the  tumor  is  unilateral,  but  may  affect  both 
lobes ;  the  enlargement  may  be  as  large  as  a  hen 's  egg  or 
even  greater,  being  sometimes  hard,  at  others  soft. 

Cancer  of  the  thyroid  has  a  tendency  to  invade  the 
neighboring  tissue ;  the  trachea,  the  larynx  and  the  esoph- 
agus are  compressed  by  the  neoplasm,  causing  ulceration 
and  perforation. 

Thyroid  cancer  is  a  tubular  epithelioma  characterized 
by  the  development  of  narrow  spaces  tilled  with  polygonal 
cells,  there  being  many  grades  between  an  adenoma  and  a 
true  cancer. 


CANCER    OF    THE    THYEOID. 


141 


The  tumor  generally  develops  in  a  preexisting  goitre, 
probably  remaining  latent  for  some  time,  then  developing 
rapidly,  the  patient  dying  in  five  or  six  months.  During 
the  course  of  the  disease  many  of  the  symptoms  of  Base- 
dow's disease  occur,  at  other  times  the  patient  complains 
of  heat  and  of  sudden  congestions  of  the  head,  accom- 


Fig.     34. — Columnar    celled    Carci- 
noma  of   Thyroid   Gland. 


Fig.  35. — Adeno  Carcinoma  of 
Thyroid   Gland. 


panied  occasionally  by  a  temperature  of  38  or  39  degrees 
C. ;  also  the  urine  shows  increased  nitrogen  elimination, 
albumin  or  sugar  as  in  Basedow's  disease.  There  are  no 
premonitory  symptoms,  the  patient  seeking  advice  on  ac- 
count of  the  rapid  increase  in  size  of  the  existing  goitre. 
Owing  to  the  rapidity  of  the  growth  of  the  tumor  and 
its  invasion  of  the  neighboring  organs,  the  patient  suffers 
from  great  functional  disturbance,  the  pain  radiates  to  the 
lower  jaw,  the  teeth,  the  neck,  the  temples,  the  ears  or 
towards  the  hands;  violent  pains  of  the  stomach  are  not 
uncommon,  probably  due  to  pressure  on  the  pneumo- 
gastric  nerve.  Compression  of  the  trachea  or  the  recur- 
rent laryngeals  causes  some  dyspnea  and  strident  inspira- 
tion. Should  the  esophagus  be  attacked  deglutition  is 
difficult  and  painful,  sometimes  impossible.  "When  there 
is  thrombosis  the  superficial  veins  of  the  skin  are  dilated, 
accompanied  by  edema  of  the  presternal  region. 


142  THE    THYEOID    AND    PAKATHYKOID    GLANDS. 

Rarely  does  the  patient  die  from  the  cachexia  but  by 
a  complication,  such  as  the  extension  of  the  disease  to  the 
lungs  which  can  be  recognized  by  the  blood  in  the  sputum 
or  by  a  bronchopneumonia  or  suffocation.  Ulceration  of 
the  carotids,  obliteration  of  the  jugular  vein,  ulceration 
of  the  trachea,  perforation  of  the  esophagus  and  ulcera- 
tion of  the  left  carotid  all  occurred  in  a  case  reported  by 
Poumet. 

The  diagnosis  is  difficult,  exploration  with  the  needle 
is  the  most  likely  to  give  satisfactory  results. 

The  prognosis  is  very  bad,  as  medicinal  treatment  is  of 
no  avail,  and  operation  is  hardly  likely  to  give  good  re- 
sults, considering  that  in  all  probability  the  whole  of  the 
gland  will  have  to  be  removed  and  that  the  neighboring 
tissues  are  more  or  less  involved. 

SAKCOMA  OF  THE   THYKOID. 

Sarcoma  of  the  thyroid  is  rare  and,  curiously,  seems 
to  be  more  common  in  men  than  in  women.  It  usually 
develops  between  the  ages  of  50  and  60  years.  It  differs 
from  cancer  in  that  it  attacks  healthy  glands  more  often 
than  those  affected  with  goitre.  It  may  grow  to  a  great 
size,  having  a  glossy  surface  and  being  of  a  soft  consist- 
ency. It  often  contains  cysts  or  calcareous  deposits. 
Pulsating  sarcomas  have  been  observed. 

The  tumor  develops  in  the  intervesicular  connective 
tissue  and  may  be  either  spindle  celled  or  round  celled. 
The  evolution  is  rapid,  producing  the  symptoms  of  pres- 
sure, etc.  The  patient  usually  succumbs  within  a  year  of 
the  development  of  the  disease.  The  tumor  is  usually 
accompanied  by  the  symptoms  of  Basedow's  disease.  The 
treatment  is  extirpation  but  the  prognosis  is  grave. 

HYDATID    CYSTS    OF    THE    THYKOID. 

Hydatid  cysts  of  the  thyroid  are  very  rare  and  can  only 
be  diagnosed  by  exploration.      The  syringe  will  contain 


HYDATID    CYSTS    OP    THE    THYROID.  143 

a  clear  liquid,  sometimes  purulent.  The  diagnosis  can  be 
made  with  the  microscope  and  by  chemical  examination 
for  succinic  acid. 

The  treatment  consists  in  opening  up  the  cyst  or  inject- 
ing iodin,  when  it  heals  easily ;  should  the  cyst  break  into 
the  trachea  the  prognosis  is  very  grave. 


CHAPTEK    X. 
CRETINISM. 

Myxedema,  a  disease  the  result  of  absence  or  loss  of 
function  of  the  thyroid  gland,  either  congenital  or  ac- 
quired, was  first  described  in  1873  by  Sir  William  Gull,  in 
a  paper  read  before  the  London  Medical  Society,  entitled 
"A  Cretinoid  Condition  Supervening  in  Adult  Life,"  in 
which  he  describes  the  three  principal  symptoms  as  tume- 
faction of  the  skin,  a  general  cachexia  and  a  cretinoid  con- 
dition. Four  years  later  Dr.  Ord  published  observations 
on  two  similar  cases,  with  an  autopsy  as  well  as  a  chemical 
examination  of  the  skin,  giving  the  disease  the  name  of 
myxedema,  since  which  time  the  literature  on  the  subject 
has  become  very  voluminous,  giving  a  complete  picture  of 
the  disease  and  establishing  its  symptomatology. 

Myxedema  is  subdivided  into  cretinism  (endemic  and 
sporadic),  which  are  cases  of  congenital  absence  or  loss  of 
function  of  the  gland  occurring  during  the  first  year  of 
postnatal  life.  Infantilism  is  a  term  applied  when  the 
thyroid  function  is  partially  or  completely  lost  before 
puberty.  The  term  myxedema  is  applied  to  those  cases 
where  the  function  is  lost  during  adult  life.  Between  the 
normal  condition  of  the  gland  and  its  complete  or  almost 
complete  cessation  of  function,  there  are  necessarily  an 
infinite  number  of  degrees,  producing  various  symptoms 
which  it  is  of  great  importance  to  recognize  as  pointing  to 
a  possible  relief  by  thyroid  feeding  and  which  are  classi- 
fied as  masked  myxedema.  There  is  yet  another  form  of 
infantilism  known  as  "Type  Loraine"  which  appears  to 
be  only  partially  due  to  loss  of  function  of  the  gland. 
These  various  forms  have  one  etiological  lesion  common 

144 


CEETINISM. 


145 


to  all,  viz :  the  loss  of  function  of  the  thyroid  gland,  the 
differences  being  due  to  the  age  at  which  the  disease 
occurs  and  the  amount  of  functionation  lost. 

Endemic  cretinism  occurs  in  districts  where  goitre  is 
endemic  and  almost  invariably  in  the  children  of  goitrous 
parentage;   75   per   cent  of  these  cretins   are   goitrous. 


Fig.   36.  — Cretin  with  goitre.       (v.  Brims.) 

There  is  no  reason  to  suppose  that  cases  with  the  same 
etiology  as  the  sporadic  form  may  not  occur  in  goitrous 
districts,  but  the  very  large  number  of  cretins  in  the  af- 
fected districts  is  positive  proof  that  a  connection  exists 
between  endemic  goitre  and  endemic  cretinism.  Occa- 
sionally a  child  is  born  with  a  small  goitre  and  very  rarely 
the  goitre  may  be  so  large  as  to  impede  delivery ;  in  these 
rare  cases  it  is  reasonable  to  suppose  that  there  is  an  an- 

10 


146 


THE    THYROID    AXD    PARATHYROID    GLANDS. 


tenatal  infection  of  the  fetus  through  the  mother.  In  by 
far  the  largest  number  of  cases,  however,  the  goitre  does 
not  appear  till  the  second  year  of  life,  that  is  after  wean- 
ing, when  the  infection  is  presumably  postnatal.  En- 
demic goitre  rarely  produces  myxedema  in  the  adult,  but 
it  seems  as  if  when  the  goitre  occurs  in  early  childhood 


Fig.  37. —  Cretin  with  goitre.       (v.  Mikulicz.] 

the  gland  ceases  to  functionate,  producing  the  typical 
symptoms.  In  the  25  per  cent  of  cases  which  have  no 
goitre  but  simply  an  atrophy  or  congenital  absence  of  the 
gland  it  is  evident  that  the  condition  cannot  be  due  to 
either  ante-  or  postnatal  infection,  with  the  contagium 
vivum  of  endemic  goitre,  and  it  is  presumable  that  they 
are  the  result  of  the  same  etiological  factors  which  pro- 
duce SDoradic  cretinism. 


CRETINISM. 


147 


The  etiology  of  sporadic  cretinism  is  by  no  means  defi- 
nitely settled;  a  certain  number  of  cases  may  be  due  to 
the  morphological  absence  of  the  thyroid  gland,  but  such 
a  lusus  naturae  must  be  very  rare.  In  the  previous 
chapter  on  thyroiditis  it  was  shown  that  syphilis  and 
tuberculosis  in  the  mother 
produce  a  hypothyroidea 
in  the  child  and  it  is  prob- 
able that  other  diseases, 
such  as  rheumatism,  may 
have  the  same  effect.  Alco- 
holism in  the  parents,  and 
especially  if  one  or  both 
were  under  the  influence 
of  liquor  at  the  time  of 
coition,  has  been  accused. 
Fletcher  ascribes  two  of 
his  cases  to  this  cause  and 
other  writers  about  15  per 
cent  of  all  cases.  In  Scot- 
land the  first-born  was 
often  feeble-minded  and 
known  as  a  "  daft  callant, ' ' 
which  was  popularly  sup- 
posed to  be  due  to  the  in- 
toxication of  the  parents, 
the  wedding  festivities  being  often  prolonged  for  several 
days  after  the  ceremony,  during  which  it  was  customary 
for  the  groom  and  often  the  bride  to  drink  very  freely 
of  the  national  beverage.  Consanguinity  of  the  parents, 
impressions  received  during  pregnancy  and  prolonged 
labor  have  also  been  cited  as  causes,  but  are  probably 
merely  coincidences. 

The  infectious  diseases  of  the  mother  which  have  been 
observed  as  associated  with  cretinism  in  the  child  are 


Fig.  38.— Cretin,  22  years  old. 
(v.  Wagner.) 


148 


THE    THYEOID    AND    PAEATHYEOID    GLANDS. 


tuberculosis,  erysipelas,  acute  articular  rheumatism,  ma- 
laria and  influenza,  which  are  among  the  diseases  de- 
scribed in  the  chapter  on  thyroiditis  as  producing  patho- 
logical conditions  of  the  gland.  That  the  specific  organism 
of  these  diseases  should  pass  the  healthy  placenta  and 
infect  the  fetus  is  improbable,  but  the  toxins  produced  by 

them  in  the  maternal  circula- 
tion will  certainly  circulate 
in  the  fetus  and  possibly  pro- 
duce disease  of  the  gland. 
These  conditions  will  account 
for  a  certain  number  of 
cases,  but  some  other  etiolog- 
ical cause  must  be  invoked  for 
the  majority. 

In  the  chapter  on  the  physi- 
ological experiments  on  the 
thyroid  gland  attention  was 
drawn  to  the  experiments  of 
Halstead  and  others,  who 
found  that  in  the  case  of  a  bitch 
who  had  had  two-thirds  of  her  thyroid  gland  removed  and 
who  was  impregnated  by  an  unoperated  dog  she  produced 
puppies  with  thyroid  glands  twelve  times  larger  than 
normal.  This  experiment  has  since  been  repeated  by 
Edmunds  with  the  same  results,  showing  that  nature  com- 
pensated for  the  absence  of  the  thyroid  secretion  in  the 
mother  by  stimulating  the  growth  of  the  gland  in  the 
pups.  It  is  probable  that  the  reverse  would  occur,  viz: 
that  should  the  mother  have  an  excess  of  thyroid  secretion 
the  gland  in  the  young  would  not  be  developed  and  conse- 
quently the  child  would  show  cretinic  symptoms  after 
weaning,  as  up  to  that  time  it  would  receive  a  certain 
amount  of  the  maternal  thyroid  secretion  with  the  milk. 
In  these  cases  the  child  would  be  a  cretin,  or  should  the 


Fig.  39.— Cretin.       (v.  Wagner.) 


CRETINISM. 


149 


gland  develop  to  a  certain  extent  the  symptoms  would 
decrease  in  proportion  to  the  development  of  the  gland. 

The  occurrence  of  a  cretinic  condition  without  goitre, 
where  goitre  is  endemic,  suggests  that  the  parenchy- 
matous increase  of  the  maternal  gland,  in  conjunction 
with  the  normal  hypersecretion  of  pregnancy,  prevents 
the  development  of  the  fetal  gland.  The  same  reasoning 
will  account  for  cases  of  sporadic  cretinism,  should  the 
maternal  gland  be  hyperexcited  during  pregnancy  from 
any  cause,  then  the  fetal  gland  would  fail  to  develop. 

In  support  of  this  theory  the  following  cases  have  been 
observed : 

A  lady  who  when  first  seen  was  between  50  and  60 
years  of  age,  suffering  from  a  large  bilateral  goitre,  with 
tremors,  tachycardia  and  great  depression,  giving  a  his- 
tory of  being  the  mother  of  two  girls  and  five  boys,  the 
goitre  having  begun  to  develop  after  her  third  pregnancy, 
and  to  have  steadily  progressed.  The  first  four  children 
were  normal,  the  two  girls  were  feeble-minded  and  died 
young,  while  the  youngest  boy,  though  mentally  up  to  the 
average,  weighed  at  19  years  of  age  340  pounds.  Another 
case  was  that  of  a  woman  who  had  a  goitre,  two  of  whose 
sons  were  feeble-minded  and  one  of  the  daughters  devel- 
oped a  melancholia  at  her  second  pregnancy,  recovering 
under  thyroid  treatment.  A  third  case  is  that  of  a  woman 
who  while  pregnant  with  her  youngest  child  developed  a 
large  parenchymatous  goitre  which  disappeared  a  year  or 
so  after  the  birth  of  the  child  which  was  a  typical  cretin. 

In  the  majority  of  cases  of  sporadic  cretinism  the  dis- 
ease of  ths  gland  can  be  traced  to  some  acute  postnatal 
infection  which,  producing  a  thyroiditis,  arrested  the  de- 
velopment or  partially  destroyed  the  gland.  It  is  by  no 
means  uncommon  to  get  a  history  of  the  child  having 
developed  normally,  both  mentally  and  physically,  till  a 
few  months  after  some  sickness,  from  which  time  it  has 


150 


THE    THYEOID    AND    PAEATHYEOID    GLANDS. 


ceased  to  grow  and  the  symptoms  of  cretinism  to  appear. 
The  older  the  child  at  the  time  of  the  arrest  of  the  thyroid 
function  the  more  incomplete  are  the  symptoms  and  the 
more  difficult  to  trace  their  true  cause. 

The  etiology  of  infantilism  is  the  same  as  that  of  cret- 
inism, except  that  it  is  probably  never  congenital,  the 
lesion  of  the  thyroid  only  taking  place  after  infancy,  the 
function  of  the  gland  being  decreased  and  not  entirely 
destroyed. 

In  myxedema  in  the  adult  the  cause  is  the  same,  being 
a  progressive  arrest  of  function  of  the  thyroid  gland,  the 
result  of  some  disease  or  traumatism.  Women  are  much 
more  liable  to  this  disease  than  men,  the  proportion  being 


Fig.  40.— Acute  thyroiditis. 


Fig.  41. — Suppurative  struma  of  Thy- 
roid gland. 


about  five  to  one,  while  in  cretinism  and  infantilism  the 
sexes  are  about  equal.  The  susceptibility  of  women  to  this 
disease  is  no  doubt  the  result  of  the  strain  thrown  upon 
the  gland  by  menstruation  and  pregnancy,  the  hyper- 
activity producing  cell  fatigue  with  a  resulting  atrophy. 
Hun  and  Prudden  state  that  64  married  women  with 
myxedema  had  300  children  and  29  abortions,  and  prob- 
ably not  all  the  abortions  were  admitted  by  the  patients ; 
but  of  78  patients  there  were  only  14  unmarried. 


CRETINISM.  1 5 1 

Pathology.— The  indispensable  lesion  necessary  to  pro- 
duce myxedema  in  any  of  its  forms  is  an  abnormality  of 
the  thyroid  gland  involving  loss  of  function.  Formerly 
the  absence  or  pathological  condition  of  the  gland  was 
regarded  as  accidental  and  not  connected  with  the  symp- 
toms, but  since  the  work  of  Gull,  Ord,  Schifr",  Riverdin, 
and  Kocher  it  has  been  recognized  as  the  essential  cause 
of  the  disease.  The  British  commission  on  myxedema  de- 
clared in  1884  that  there  was  but  one  constant  anatomical 
lesion  in  myxedema,  the  atrophy  or  abolition  of  function 
of  the  thyroid  gland. 

The  abolition  of  function  may  be  due  to  degeneration 
(goitre)  or  to  atrophic  sclerosis.  Bramwell  describes  44 
cases  of  myxedema  with  10  autopsies,  in  9  of  which  no 
trace  of  the  thyroid  could  be  found  and  in  the  tenth  the 
lobe  was  the  seat  of  a  tumor,  which  was  either  congenital 
or  followed  some  infectious  disease.  In  many  cases  the 
thyroid  is  represented  by  a  mass  of  connective  or  of  adi- 
pose tissue,  the  thyroid  arteries  being  absent.  In  endemic 
cretinism  25  per  cent  of  the  cases  show  no  trace  of  gland 
tissue,  it  being  replaced  by  connective  tissue ;  in  the  other 
75  per  cent  the  secretion  is  suppressed  or  perverted,  due 
to  a  degeneration  of  the  gland. 

Virchow  claimed  that  the  mental  deficiency  in  cretinism 
was  due  to  premature  ossification  of  the  sphenobasilar 
bone,  preventing  the  elongation  of  the  base  of  the  skull ; 
others  contended  that  the  pressure  of  the  goitre  on  the 
carotid  arteries  prevented  a  sufficient  blood  supply  to  the 
brain,  and  that  the  nongoitrous  cases  were  due  to  insuffi- 
cient cerebral  circulation,  from  narrowing  of  the  cranial 
foramina  and  other  causes.  Malcarne  counted  the  lamellae 
of  the  cerebellum  and  found  only  300  instead  of  the  normal 
600;  this  observation  was  confirmed  by  others. 

Ord,  Virchow  and  Horsley  examined  the  tissues  micro- 
scopically and  failed  to  find  any  trace  of  acini  or  of  thyroid! 


152 


THE    THYROID    AND    PAEATHYEOID    GLANDS. 


cells,  only  a  mass  of  connective  tissue  occupying  the  posi- 
tion of  the  gland.  Stilling  found  the  same  condition  and 
also  the  absence  of  the  thyroid  artery.  Langhans  sug- 
gested a  process  of  interstitial  inflammation  of  the  gland 
with  infiltration  of  the  embryonic  cells,  absolutely  compar- 
able with  cirrhosis  of  the  liver, 
the  sclerotic  tissue  developing 
little  by  little,  the  vessels  suc- 
cumbing to  endarteritis  obliter- 
ans, the  acini  atrophying  and  dis- 
appearing. The  British  com- 
mission decided  that  the  inflam- 
mation commenced  in  the  parietal 
vessels,  infiltrating  the  embryonic 
cells,  which  inflammation  was 
accompanied  by  a  proliferation 
of  the  endothelium,  destroying 
the  vessel  walls.  Under  these  con- 
ditions the  epithelium  of  the  acini 
proliferate,  the  connective  tissue 
of  the  gland  and  the  parietes  of 
the  acini  become  congested  with 
embryonic  cells  which  slowly 
transform  into  sclerotic  tissue. 
The  sclerosis  little  by  little  stifles 
the  glandular  tissue,  which  takes  on  the  appearance  of 
islets,  which  gradually  disappear;  in  short,  there  is  an 
atrophy  from  interstitial  inflammation  which  develops 
.slowly  toward  a  final  sclerosis  and  thus  to  the  suppression 
of  the  function  of  the  gland.  Coulon  examined  six  cases 
and  found  that  in  no  case  was  the  thyroid  entirely  absent, 
but  that  there  were  tissue  and  cytological  changes,  which 
showed  that  the  gland  had  almost,  if  not  entirely,  ceased 
to  functionate,  the  acini  being  very  few  and  small,  appar- 
ently containing  little  or  no  colloid,  while  there  was  a  great 


.Fig.  42. — Atrophic  gland  from 
a  case  of  myxedema. 


CRETINISM.  153 

increase  of  connective  tissue.  Other  investigators  have  in- 
variably found  little  or  no  normal  tissue  in  the  gland. 

In  cretins  persistent  thymus  is  not  uncommon,  the  hypo- 
physis cerebri  is  sometimes  enlarged,  sometimes  atrophied. 
An  observation  of  great  interest  is  that  the  thyroid  can  be 
atrophied  in  cases  when  the  mentality  is  nearly  normal, 
though  the  physical  condition 
may  be  distinctly  cretinic. 
This  observation  and  the  re- 
sults of  physiological  experi- 
ments with  extirpation  of  the 
thyroid  and  parathyroids 
has  led  Brissaud  to  advance 
the  theory  that  the  thyroid 
gland  has  to  do  with  the 
physical  and  the  parathy- 
roids with  the  mental  de- 
velopment.      Murray    is    of 

opinion  that  the  parathyroids  have  to  do  with  the  nervous 
symptoms  and  the  thyroid  with  the  nutrition  and  assimila- 
tion. 

Coulon  points  out  that  in  the  lower  type  of  cretins  the 
small  amount  of  colloid  present  is  of  such  a  consistency  as 
to  be  unable  to  pass  into  the  lymphatics  while  in  the  higher 
types  the  colloid  is  mere  fluid. 

The  skin  is  in  a  thickened  pseudoedematous  condition; 
there  is  hypertrophy  of  the  connective  tissue  with  atrophy 
of  the  sebaceous  sudoriferous  glands  and  hair  follicles ;  on 
microscopical  examination  there  appears  to  be  an  increase 
of  connective  tissue  reverted  to  an  embryonic  type;  the 
fibrils  are  disassociated  and  separated  by  a  substance 
which  is  said  to  be  mucin ;  the  fibres  and  fibrils  of  the  con- 
nective tissue  are  gelatinous  and  swollen;  the  interstitial 
lymphatic  spaces  are  enlarged;  the  cells  are  hyper- 
trophied;  the  nuclei  enlarged;  in  fact,  a  return  of  the 


154  THE    THYB0ID    AND    PAEATHYEOID    GLANDS. 

tissue  to  an  embryonic  state.  Virchow  considers  that  it 
is  not  a  regressive  bnt  an  irritative  process,  analogous  to 
phlegmasia  dolens  or  elephantiasis,  justifying  Charcot's 
nomenclature  of ' '  pachydermia ' '  The  subcutaneous  layer 
of  fat  is  often  very  thick.  The  cutaneous  vessels  partici- 
pate in  the  general  condition,  the  walls  are  thickened,  their 
lumen  reduced,  progressing  to  obliteration. 

Kopp,  a  pupil  of  Langhans,  found  thickening  of  the 
walls  of  the  vessels  in  the  nerve  trunks,  and  also  in  the 
peripheral  nerves,  the  lymph  spaces  were  enlarged,  con- 
taining edematous  vesicles  and  fusiform  cells.  Schultz 
and  Eenant  claim  that  these  findings  are  not  pathognomic 
as  they  are  found  in  the  normal  cases  as  well  as  in  various 
diseases. 

In  the  central  nervous  system  Hamilton  and  Roggo  witch 
describe  alterations  in  the  brain;  Custue  in  the  horns  of 
the  spinal  cord;  Hadden  in  the  sympathetic.  De  Quer- 
vain,  who  examined  the  nervous  system  of  thyroidecto- 
mized  monkeys,  dogs  and  cats,  came  to  the  conclusion  that 
these  lesions  are  not  constant,  and  that  there  is  no  path- 
ognomic lesion  of  the  central  nervous  system  in  myxedema. 

Mendil,  Lickenstein,  Schotten  and  Kraeplin  have  ex- 
amined the  blood  and  have  found  a  diminished  amount  of 
hemoglobin  (65  to  68  per  cent),  the  diameter  of  the  red 
corpuscles  seemed  to  be  increased  (8/*  to  10/*),  nucleated 
reds  were  found  and  in  some  cases  a  slight  leucocytosis. 
The  coagulability  of  the  blood  was  reduced.  The  blood  is 
poor  in  proteids  and  inorganic  salts. 

In  cretinism  and  in  cases  of  infantilism  Hofmeister 
found  an  arrest  of  development  of  the  skeleton ;  exact  ex- 
periments  made  on  animals  showed  that  the  long  bones, 
the  vertebral  column  and  the  pelvis  were  one-third  less 
than  in  the  control  animals,  the  head  alone  developing  nor- 
mally. The  epiphyseal  nucleus  remains  cartilaginous, 
failing  to  ossify,  explaining  the  rachitic  appearance. 


CRETINISM.  155 

In  advanced  cases  of  myxedema  there  is  often  hyper- 
trophy of  the  left  heart,  while  chronic  nephritis  may  de- 
velop and  true  edema  appear. 

Symptoms.— When  cretinism  is  fully  developed  during 
intrauterine  life,  which  is  very  rare,  it  usually  results  in 
the  death  of  the  fetus,  which  displays  a  curious  stunted 
conformation  of  body  with  redundant  skin,  thickened  cra- 
nial bones,  imperfectly  formed  face  and  a  general  irregu- 
larity of  development.  Those  who  are  unfortunately  born 
alive  present  a  remarkable  picture  of  mental  and  physical 
deformity,  being  dwarfed  monstrosities  with  vegetative 
intellects.  The  fontanelles  are  larger  than  normal,  the 
hair  thick  and  descending  towards  the  eyebrows,  so  that 
the  forehead  appears  small,  the  eyes  are  dull  and  expres- 
sionless, being  usually  half  closed;  the  lids  heavy  and 
swollen,  with  only  a  few  eyelashes ;  the  skin  is  livid  during 
the  first  month,  later  becoming  a  dingy  yellow ;  the  nose  is 
flat,  the  mouth  large,  the  tongue  dry  and  protruding  from 
the  mouth,  the  lips  thickened  and  purple,  the  lower  one 
being  pendulous,  over  which  the  saliva  flows  continuously. 
The  cries  are  harsh  and  unnatural;  they  take  the  breast 
sluggishly  but  never  refuse  it,  appearing  to  be  never  sat- 
isfied. Should  they  survive  they  develop  into  the  lowest 
form  of  cretinism. 

As  a  rule  however,  in  both  sporadic  and  endemic  forms 
there  are  usually  ?no  symptoms  apparent  at  the  birth  of 
the  child,  nor  do  they  appear  till  the  sixth  or  seventh 
month,  the  thyroid  secretion  being  probably  supplied  from 
the  mother  through  the  milk.  About  the  time  of  weaning 
it  is  observed  that  the  child  appears  dull  and  that  there  is 
a  want  of  proportion  in  the  growth  of  the  limbs  and  trunk, 
the  head  being  proportionately  much  larger  than  the  rest 
of  the  members.  As  the  child  ages  these  symptoms  be- 
come much  more  marked,  the  extremities  becoming  short 
and  stumpy,  the  subcutaneous  tissue  thick  and  baggy  and 


156 


THE    THYEOID    AND    PAEATHYEOID    GLANDS. 


a  goitre  may  develop  with  great  rapidity.  The  facies  are 
characteristic,  the  head  is  out  of  proportion  to  the  body, 
with  frontal  insufficiency  and  occipital  flattening ;  the  f  on- 
tanelles  remain  open  until  the  eighth  or  ninth  year,  and 
sometimes  into  adult  life ;  the  forehead  is  low,  the  base  of 
the  nose  broad,  the  eyes  wide  apart  and  expressionless 
and  half  closed,  with  thickened  lid  and  scanty  eyebrows ; 
the  lips  are  thick  and  purple,  the  lower  lip  pendulous  with 


Fig.  44.  Fig.  45. 

A  case  of  sporadic  cretinism  before  and  after  thyroid  feeding. 

(v.  Bruns.) 


the  saliva  running  over  it;  the  tongue  swollen  and  pro- 
truding, the  cheeks  baggy,  of  a  dirty  icteroid  hue,  with- 
out the  red  patch  of  health.  The  teeth  are  sometimes 
absent  or  the  first  dentition  appears  late,  decaying  and 
falling  out  early.  There  may  be  no  second  dentition  or  it 
may  be  late  in  appearing,  the  teeth  being  irregular  and 
poorly  developed,  decaying  and  falling  out  early;  the 
lower  jaw  may  either  protrude  or  retreat,  but  is  rarely 
normal;  there  is  tumefaction  of  the  nasal  mucous  mem- 
brane causing  mouth  breathing ;  the  ears  are  thickened  and 


CRETINISM.  1  0  ( 

either  waxy  or  purple  in  appearance.  Fatty  tumors  are 
common  in  the  older  children,  but  wanting  in  infants ;  they 
appear  in  the  supraclavicular  region  behind  the  sterno- 
cleidomastoid muscle  in  the  axilla,  between  the  scapulae, 
and  in  other  parts  of  the  body,  being  often  symmetrical 
and  attaining  at  times  the  size  of  a  hen's  egg.  The  neck 
is  short  and  thick,  often  with  a  depression  above  the 
suprasternal  notch.  In  the  endemic  form  goitre  is  present 
in  75  per  cent  of  the  cases  and  is  nearly  always  due  to 
postnatal  infection;  very  rarely  are  infants  born  with  a 
goitre.  The  spine  is  crooked,  having  a  posterior  curva- 
ture in  the  cervical  region,  probably  owing  to  weakness 
of  the  muscles  and  a  compensating  anterior  curvature  in 
the  lower  dorsal  and  lumbar  region,  causing  the  abdomen 
to  protrude;  there  is  also  a  lateral  curvature  developed. 
A  pseudoumbilical  hernia  is  generally  present  but  con- 
tains no  gut ;  true  inguinal  hernia  is  not  uncommon.  The 
genitalia  are  usually  small  and  poorly  developed,  often 
with  various  deformities,  the  testicles  do  not  descend  until 
late  and  sometimes  not  at  all ;  the  head  of  the  clitoris  is 
enlarged,  looking  like  a  penis  between  the  edematous  labia 
major  a. 

The  arms  are  thick,  short  and  puffy,  the  fingers  are 
thickened,  the  legs  are  cylindrical,  giving  the  impression 
of  props,  or  they  may  be  bent,  resembling  rickets ;  the  feet 
are  short  and  deformed,  being  too  wide  for  the  length, 
the  great  toe  being  swollen.  The  nails  on  both  hands  and 
feet  are  brittle  and  atrophied  or  may  only  be  rudimentary. 
The  mucous  membranes  are  tumefied,  dry  and  pale,  the 
buccal  mucous  membrane  swollen,  as  is  also  the  palate  and 
pharynx,  the  esophagus,  stomach,  intestines  and  rectum 
present  a  similar  appearance,  which  accounts  for  the  poor 
digestion,  assimilation  and  severe  constipation,  with  occa- 
sional attacks  of  diarrhea.  There  is  edema  of  the  glottis, 
the  gums  are  puffy,  bleeding  easily;  the  tongue  is  swollen, 


158 


THE    THYEOID    AND    PAKATHYROID    GLANDS. 


accounting  for  the  thick,  peculiar  character  of  the  speech. 
The  skin  is  dry,  harsh,  scaly  and  thickened,  sometimes 
over  the  whole  body,  with  a  baggy  appearance  as  if  it  were 
too  large  for  its  contents;  the  thickening  may  be  only  in 
patches.  At  first  sight  the  condition  of  the  skin  suggests 
edema,  but  as  on  pressure  it  does  not  pit,  clears  up  the 
diagnosis ;  there  is  little  or  no  perspiration  and  the  seba- 


Fig.  46.  Fig.  47. 

A  case  of  sporadic  cretinism  aged  6  years  before  and  after  thyroid 
feeding,  in  the  author's  practice. 

ceous  glands  fail  to  secrete,  the  skin  is  free  from  down, 
the  pubes  and  axillae  may  be  hairless  or  the  covering 
sparse,  not  appearing  till  very  late;  the  beard  is  usually 
absent  as  are  also  the  eyebrows  and  eyelashes;  the  hair 
of  the  head  is  coarse,  harsh  and  scant,  receding  from  the 
temples,  or  the  middle  line,  the  scalp  is  more  or  less  bald ; 


CRETINISM.  159 

there  may  be  bald  patches  in  various  parts  of  the  head; 
sometimes  the  hair  is  very  abundant. 

The  physical  development  is  arrested,  cretins  of  15 
years  of  age  may  be  no  more  than  two  feet  six  or  three  feet 
high;  the  lips,  nose,  ears,  hands  and  feet  are  cold,  the 
temperature  is  subnormal,  and  they  are  very  susceptible 
to  cold.  The  respiration  is  slow.  The  digestion  is  very 
indifferent,  the  food  being  only  partially  digested,  the 
feces  containing  undigested  proteid,  starch  and  fats ;  the 
appetite  is  usually  moderate,  but  there  is  a  repugnance  to 
meat,  which  is  fortunate,  as  it  is  not  well  borne.  It  will  be 
remembered  that  in  a  previous  chapter  the  feeding  experi- 
ments on  thyroidectomized  animals  showed  that  proteid 
diet  increased  the  symptoms.  Mentally  their  develop- 
ment is  very  varied ;  in  the  lowest  types  voluntary  move- 
ment does  not  exist  nor  is  there  any  mentality,  the  facul- 
ties being  purely  vegetative,  "l'homme  plante."  Others 
again  are  vegetative  and  reproductive,  "l'homme  ani- 
mal. ' '  Their  eyesight  is  generally  fair,  but  their  hearing 
is  often  defective.  Niepee  found  the  auditory  foramen  con- 
tracted and  the  ossicles  large  and  spongy.  The  intellect- 
ual faculties  are  very  limited,  as  a  rule,  though  by  train- 
ing some  few  can  be  taught  to  take  some  care  of  them- 
selves and  to  articulate  a  few  words  which  they  accom- 
pany with  exaggerated  and  ungainly  gestures.  They  are 
dull,  stupid  and  indifferent  to  their  surroundings;  some 
are  passionate  and  excitable,  being  guided  in  their  emo- 
tions rather  by  instinct  than  by  reason ;  they  are  capable 
of  a  certain  amount  of  training  and  though  their  affec- 
tions are  not  deep  they  form  attachments  to  those  who 
minister  to  their  wants.  Puberty  is  delayed  and  may 
never  occur  at  all.  Broca  states  that  in  true  cretinism  it 
never  occurs.  Masturbation  is  the  exception,  most  of 
them  having  no  sexual  desire ;  a  few  have  paroxysms  of 
great  sexual  excitement.      The  disease  progresses  slowly 


160 


THE    THYROID    AND    PARATHYEOID    GLANDS. 


with  no  tendency  to  improvement;  they  are  not,  however, 
very  susceptible  to  the  diseases  of  childhood,  but  usually 
succumb  to  some  pulmonary  trouble  before  20  years  of 


Fig.  48.  —Cretin,  aged  12  years,  with  the  permission  of  Dr.  A.  C.  Roger, 

Fairbault,  Minn. 

age,  a  few  live  till  40  or  even  longer.  Rachitis  is  a  com- 
mon complication;  in  fact,  it  is  said  that  all  cretins  are 
rachitic,  but  this  is  highly  improbable,  the  nondevelop- 
ment  and  ossification  of  the  epiphyseal  nuclei  being  mis- 


CRETINISM    IN    ANIMALS. 


161 


taken  for  rachitis  which  it  closely  resembles.  Asthma  is 
a  common  complication,  possibly  due  in  a  certain  number 
of  cases  to  persistent  thymus. 

The  blood  is  low  in  hemoglobin  and  in  red  blood  cor- 
puscles, while  the  arterial  blood  is  of  a  venous  hue  from 
its  containing  a  reduced  quantity  of  oxygen. 

The  most  marked  symptom  is  the  shortness  of  stature, 
in  illustration  of  which  Hertoghe,  of  Antwerp,  quotes  a 
case  which  had  not  grown  since  his  twelfth  year,  who  at 
27  was  four  feet  six  inches  high  and  weighed  81  pounds, 
and  who  grew  one  inch  in  three  months  on  thyroid  treat- 
ment, and  another  who  had  not  grown  since  his  four- 
teenth year  and  at  18  was  five  feet  one  inch,  weighing 
110  pounds.  In  these  cases  the  arrest  of  growth  had  com- 
menced about  puberty,  the  patient  ceasing  to  increase  in 
height  but  gaining  in  weight. 

CRETINISM    IN    ANIMALS. 

Cretinism  in  animals  has  occasionally  been  recorded. 
Eberth  in  1878  described  a  monster  calf  which  he  consid- 
ered a  cretin.  Ghirlt  in  1877  describes  a  few  cases.  In 
South  Kensington  Museum  there  is  a  stuffed  specimen 
and  the  Koyal  College  of  Surgeons  possesses  the  skeleton 
of  a  typical  cretin  calf. 

Cretinism  appears  to  occur  with  curious  frequency  in 
Dexter-Kerry  cattle,  a  breed  which  has  become  popular  in 
Engand  in  recent  years.  C.  G.  Selegmann  in  the  Journal 
of  Pathology  and  Bacteriology  for  March,  1904,  describes 
the  occurrence  of  cretins  in  the  herds  of  this  particular  breed. 
They  are  usually  born  prematurely,  with  short-rounded 
head,  depressed  nostrils  and  projecting  mandible,  combined 
with  extreme  shortness  of  the  limbs.  They  have  been 
christened  ' '  bull  dog  calves ' '  by  the  herdsmen.  They  seem 
to  occur  with  considerable  frequency  in  all  herds  of  this 
breed  irrespective  of  locality.  In  1891  one  herd  produced 
li 


162 


THE    THYROID    AND    PARATHYROID    GLANDS. 


seven  cretins  out  of  twenty  births,  or  35  per  cent,  another 
herd  produced  twenty-seven  calves,  five  of  which  were 
cretins  or  18.5  per  cent.  The  pregnancies  of  the  cows  are 
abnormal;  the  calf  is  usually  dropped  about  the  sixth, 
seventh  or  eighth  month,  the  cow's  belly  begins  to  swell, 
becoming  enormously  distended,  before  the  cretin  is  born ; 


~--~ 


Fig.  49.— Skull  of  Cretin  calf.      (C.  G.  Selegmann. ) 


the  cow  loses  a  large  quantity  of  water,  decreasing  in  size 
before  labor.  When  this  occurs  months  or  weeks  before 
labor,  a  further  abnormal  increase  followed  hj  sl  decrease 
may  occur.  After  the  birth  the  lochia  is  more  abundant. 
The  placenta,  instead  of  coming  away  in  from  one  half 
to  four  hours  after  delivery  as  normally,  is  got  rid  of 
slowly  and  in  fragments,  the  process  often  lasting  two  or 


CEETINISM    IN    ANIMALS.  163 

three  days.  The  thyroids  of  the  cretin  calves  examined 
were  represented  by  a  couple  of  more  or  less  rounded 
edematous  dark  purple  colored  masses  one  on  each  side 
of  the  trachea,  the  isthmus  being  absent.  On  microscop- 
ical examination  the  cells  appear  to  be  only  partially  or 
not  at  all  arranged  in  vesicles,  usually  forming  irregular 
masses  or  branching  columns  with  or  more  frequently 
without  a  lumen.  Colloid  is  commonly  absent,  occasion- 
ally present  in  a  few  vesicles  only.  Injection  of  the  gland 
substance  into  cats  did  not  produce  the  typical  fall  in 
blood  pressure.  These  observations  of  Selegmann  are  of 
great  interest  and  further  investigation  may  show  that 
sporadic  cretinism  may  be  due  to  placental  disease. 


CHAPTER    XL 

MYXEDEMATOUS    INFANTILISM. 

Myxedematous  infantilism  has  been  defined  as  an 
anomaly  of  development  characterized  by  the  persistence 
after  puberty  of  the  morphological  characters  of  child- 
hood, the  arrest  of  the  physical  development  being  often 
accompanied  by  a  general  mental  deficiency  corresponding 
to  the  physical  retardation. 

In  1871  Faneau  published  an  article  on  femininism  and 
infantilism  in  the  tuberculous.  Joffroy,  Bourneville, 
Sollier,  Souques,  Barety,  Fere,  Marfans,  Gruinon,  Capitan, 
Kicher,  Gerard  and  others  published  reports  of  interesting 
cases  of  femininism,  infantilism  and  senilism,  but  these 
forms  were  not  recognized  in  medical  literature  till  the 
last  decade,  when  Brissaud  and  Hertoghe,  of  Antwerp,  de- 
scribed the  etiology,  symptoms  and  treatment.  In  1894 
Brissaud,  in  his  lectures  on  myxedema  and  cretinism,  at 
the  Saltpetriere  described  a  less  severe  form  of  cretinism, 
consisting  of  a  partial  arrest  of  physical  and  mental  devel- 
opment, at  the  same  time  showing  to  his  class  a  boy  of  18 
suffering  from  thyroid  insufficiency,  who  presented  all 
the  symptoms  of  infantilism.  Miege  in  1895  described  the 
condition  of  the  genital  organs  in  these  cases  and  drew 
attention  to  their  arrested  development,  pointed  out  that 
many  of  the  cases  whose  want  of  development  was  attri- 
buted to  congenital  syphilis,  or  to  tuberculosis  were  really 
suffering  from  hypothyroidea,  drawing  attention  also  to 
the  possible  connection  of  giantism,  dwarfism,  rachitis  and 
obesity  with  an  abnormal  functionation  of  the  thyroid 
gland.  Hertoghe  published  his  observations  in  the  same 
field,  assuring  that  there  was  no  infantilism  without  insuf- 

164 


INFANTILISM. 


165 


ficiency  of  the  thyroid  gland.  Hofmeister,  G-ley,  Broca, 
Brissaud  and  others  followed,  showing  in  the  most  conclu- 
sive manner  the  important  part  played  by  the  thyroid 
gland  in  physical  and  mental  development. 

The  etiology  of  infantilism,  to  be  more  definite,  myxe- 
dematous infantilism,  is  undoubtedly  a  lesion  of  the 
thyroid  gland  which  has  resulted  in  a  deficient  secretion. 
The  cause  of  this  lesion  may  be,  though  probably  very 
rarely,  the  result  of  partial  sclerosis  of  the  gland  from 
hereditary  syphilis  or  tuberculosis,  but  in  the  vast  ma- 
jority of  cases  it  will  be  found  on  obtaining  the  history  of 
the  case  that  the  patient  has  suffered  from  some  acute 
disease  in  childhood  which  has  affected  the  gland,  pro- 
ducing a  so  considerable  sclerosis  that  it  is  incapacitated 
from  secreting  sufficient  for  the  needs  of  the  organisms. 

The  symptoms  of  infantilism  are  those  of  cretinism  in 
an  attenuated  form,  varying  with  the  age  at  which  the 
disease  commenced,  and  the  amount  of  the  destruction  of 
tissue  in  the  thyroid  gland.  The  following  symptoms 
may  appear  but  will  never  or  rarely  all  be  found  in  a 
single  case.  "When  the  physician  is  consulted  upon  the 
nondevelopment  of  a  patient,  if  he  finds  a  few  of  these 
symptoms,  especially  if  coupled  with  the  history  of  an 
acute  disease  antedating  the  commencement  of  the  arrest 
of  development,  he  is  justified  in  prescribing  thyroid 
feeding. 

The  patient  appears  old  for  his  years,  short  in  stature 
but  usually  of  symmetrical  proportions,  though  stout  and 
heavy.  The  face  is  large,  round  and  moonlike,  with  a 
stupid  surly  expression,  pale  and  waxy  looking,  the  scalp 
and  the  skin  of  the  face  are  thickened,  the  eyes  somewhat 
wide  apart,  the  mouth  large,  the  nose  broad,  the  hair  is 
usually  abundant  but  coarse  up  to  about  the  twentieth 
year,  when  baldness  commences,  the  mucous  membranes 
are  turgid,  especially  in  the  nasal  passages  and  larynx, 


166 


THE    THYKOID    AND    PAKATHYEOID    GLANDS. 


causing  mouth  breathing  with  a  peculiar  harsh  nasal  into- 
nation as  if  the  patient  were  suffering  from  a  severe  cold ; 


Fig.  50.  — Before  treatment. 
(Hertoghe.) 


Fig.  51.— After  6  months'  treat- 
ment.    (Hertoghe.) 


the  tongue  may  be  swollen,  which  has  a  characteristic 
effect  upon  the  articulation.     The  neck  is  short  and  thick, 


INFANTILISM. 


167 


the  body  usually  well  nourished,  but  there  is  a  thickening 
of  the  skin  which  disguises  the  outlines  of  the  muscles  and 


Fig.  52.— After  1  year's  treatment.  Fig.  53.— After  2  years'  treat- 

(Hertoghe.)  ment.      (Hertoghe.) 

bones.      The  hands  are  thick  and  of  a  bluish  tinge,  the 
veins  being  distended.     The  feet  are  flat,  short  and  broad. 


168 


THE    THYEOID    AND    PAEATHYEOID    GLANDS. 


The  hands  and  feet  are  cold,  suffering  from  chilblains  in 
winter  and  fetid  perspiration  in  summer.  The  skin  is  dry 
and  harsh,  perspiration  being  absent  or  subnormal.  The 
organs  of  generation  remain  infantile,  at  23  there  may  be 
no  more  sexual  development  than  in  a  normal  child  of  10. 
In  females  menstruation  is  delayed  and  even  when  estab- 
lished is  scant,  irregular  and  painful.  The  nondevelop- 
ment  of  the  sexual  organs  is  one  of  the  most  constant  and 
important  symptoms  from  the  diagnostic  standpoint, 
though  occasionally  the  organs  may  be  normal.     The  teeth 

are  small,  irregular  and  decay 
early.  If  the  disease  com- 
mences in  early  childhood,  the 
abdomen  may  protrude  and 
there  may  be  a  slight  pseudo- 
umbilical  hernia.  The  limbs 
are  often  round  and  straight, 
having  the  appearance  of 
columns.  There  is  a  persist- 
ence of  the  epiphyseal  cartil- 
ages which  can  be  distinctly 
seen  with  the  X-rays. 

The  mentality  is  sometimes 
apparently  not  impaired,  the 
child  being  equal  to  the  aver- 
age ;  in  other  cases  he  is 
mentally  dull  and  can  only  be  taught  to  read  and  write 
with  difficulty.  This  difference  between  the  physical  and 
mental  development  has  caused  some  observers  to  come 
to  the  conclusion  that  on  the  thyroid  gland  depends  the 
physical  growth  while  the  mental  development  is  asso- 
ciated with  the  parathyroids. 

There  is,  however,  a  want  of  mental  development  in  the 
childishness  of  the  patients ;  although  their  education  may 
be  up  to  the  average  there  is  an  arrest  of  development  in 


Fig.  54. —  Skiagram  of  the  hand 
of  a  type  Loraine,  17  years  old. 


INFANTILISM. 


169 


ideas  and  mode  of  thought ;  they  are  childlike  in  manners, 
easily  provoked  to  tears  or  laughter,  associating  with  those 
much  younger  in  years  and  continuing  to  take  interest  in 
the  amusements  of  children;  often  there  is  a  certain 
amount  of  effeminacy  which  suggests  sexual  perversion. 


Tig.  55. —  Skiagram  of  the  hand  of  a    Fig.  56. — Skiagram  of  the  hand  of  a 
normal  child,  6  years  old.  case  of  myxedema,  19  years  old. 


The  pulse  and  temperature  are  usually  normal,  but  the 
respiration  is  often  labored  and  noisy,  due  to  adenoids  or 
to  hypertrophy  of  the  mucous  membranes  of  the  air  pas- 
sages. 

Albuminuria  and  rachitis  are  two  diseases  which  may 
exist  with  thyroid  insufficiency,  the  former  may  disappear 
under  treatment.  There  is  also  a  hyperazoturia  occurring 
at  intervals,  owing  to  a  retention  of  nitrogen. 

In  weighing  the  symptoms  in  these  cases  the  age  at 
which  the  disease  developed  has  to  be  taken  into  consid- 
eration, the  older  the  child  at  the  commencement  of  the 
disease  the  more  obscure  and  atypical  will  be  the  symp- 
toms. 

Infantilism  of  the  type  Loraine  has  been  described  by 


170 


THE    THYROID   AXD    PAEATHYEOID    GLAXDS. 


Brissaud,  Loraine,  Faneau  de  la  Cour  and  others  as  a 
particular  form  of  arrested  development,  differing  from 
myxedematous  infantilism  in  many  points,  and  appears  to 
be  due  to  a  congenital  nondevelopment  of  the  arteries, 
sometimes  combined  with  thyroid  insufficiency.  Admit- 
ting that  there  is  such  a  con- 
dition as  congenital  nonde- 
velopment of  the  arteries,  in 
which  the  aorta,  the  renal  and 
pulmonary  arteries,  etc.,  are 
reduced  in  size,  it  is  evident 
that  with  the  other  organs 
the  thyroid  will  not  receive 
sufficient  nourishment  and 
will  consequently  be  arrested 
in  its  growth  and  functiona- 
tion.  Much  has  been  written 
for  and  against  the  existence 
of  a  condition  of  congenital 
narrowing  or  arrest  of  de- 
velopment of  the  aorta  and 
blood  vessels,  but  there  seems 
to  be  no  reason  why  such  a  condition  should  not  exist  in 
the  blood  vessels  as  in  other  organs  of  the  body.  Suter, 
in  the  "Archives  of  Exp.  Path,  and  Pharm., "  vol.  xxxix, 
holds  that  there  is  no  such  thing  as  congenital  narrowing- 
of  the  aorta  but  that  the  variation  in  calibre  found  at 
autopsy  is  merely  a  question  of  greater  or  less  elasticity ; 
in  any  case,  it  appears  that  some  aortas  are  at  least  more 
elastic  than  others.  Ohlmacher,  in  his  researches  on  con- 
genital epilepsy,  found  narrowing  of  the  aorta  in  nearly 
every  case.  That  aortic  narrowing  must  have  far-reach- 
ing pathological  effects,  from  the  insufficient  blood  supply 
to  the  various  organs  and  upon  the  heart  from  the  extra 
work  thrown  upon  it,  is  evident.  A  congenital  mitral 
stenosis  would  act  in  much  the  same  manner. 


Fig.  57.—  Skiagram  of  the  hand  of 
a  type  Loraine,  16  years  old. 


IXFAXTILISM. 


171 


Fig. 


In  the  form  of  infantilism  under  discussion  there  is  an 
hypertrophy  of  the  left  ventricle  with  a  high  blood  pres- 
sure and  small  arteries,  the  pulsation  of  the  aorta  cannot 
be  felt  in  the  neck,  the  temperature  is  subnormal;  the 
physical  appearance  is  not 
that  of  myxedematous  infan- 
tilism. The  patient  is  short  of 
stature,  at  the  first  glance 
looking  like  a  boy,  but  on 
closer  observation  he  appears 
as  a  small  adult,  which  has 
been  well  described  as  a  man 
seen  through  the  large  end  of 
an  opera  glass;  the  shoulders 
are  large,  the  chest  narrow, 
the  bony  projections  well 
marked,  the  muscles  without 
being  strongly  developed  are 
distinct,  having  lost  the  fatty  covering  of  childhood.  He 
is  a  man  in  miniature  giving  the  impression  of  effeminacy 
and  debility. 

He  may  have  little  or  no  hair  on  the  face,  pubes  or  in 
the  axillae,  the  sexual  organs  are  small  but  developed  in 
proportion  to  his  size.  The  head,  which  in  the  myxe- 
dematous form  is  usually  large,  is  small,  the  face  is  often 
pitted  with  psoriasis,  the  feet  small  and  flat,  the  teeth 
decayed,  the  gums  red,  irritable  and  lined  with  tartar. 
The  fontanelles  close  early  and  the  epiphyses  ossify  nor- 
mally, differing  in  this  from  the  myxedematous  form. 
Fetid  perspiration  of  the  feet  is  common.  Nocturnal  in- 
continence of  urine  is  associated  with  this  form  of  in- 
fantilism. 

It  is  by  no  means  evident  that  this  form  of  infantilism 
is  directly  due  to  hyposecretion  of  the  thyroid  gland;  on 
the  contrary,  it  is  evident  that  the  arrested  development 


58. — Skiagram  of  a  normal 
hand,  20  years  old. 


172 


THE    THYKOID    AND    PAEATHYEOID    GLANDS. 


of  the  circulatory  system  plays  an  important  part;  other 
glands  are  probably  trophic  in  their  function,  the  testicles 


Fig.  59.  Fig.  GO. 

Infantilism  aged  19  yrs. 
Before  treatment.  After  1  year's  treatment. 

Height,  4'  6%";   weight,  76  lbs.  Height,  4'  liyz";  weight,  92  lbs. 


INFANTILISM.  173 

and  ovaries,  the  thymus,  the  suprarenals  and  the  spleen 
may  all  have  a  function  to  perform  necessary  for  the  com- 
plete and  normal  development  of  the  organism  which  has 
not  as  yet  been  discovered.  Many  of  these  cases,  however, 
improve  on  thyroid  treatment,  though  not  so  completely 
as  in  the  case  of  myxedematous  infantilism. 

If  a  skiagraph  of  the  hand  or  long  bones  is  taken  and  it 
is  found  that  the  epiphyses  are  ossified  it  is  evident  that 
increase  in  height  will  not  follow  any  treatment,  but 
should  the  intraosseous  cartilage  still  persist  the  proba- 
bilities are  that  thyroid  treatment  will  stimulate  growth. 

Anangioplasia,  or  the  congenital  diminution  of  the  lumen 
of  the  larger  arteries,  is  considered  as  a  separate  form  of 
infantilism  by  some  authors,  and  has  been  found  associ- 
ated with  the  lymphatic  constitution  in  many  cases  of  so- 
called  idiopathic  epilepsy  by  Ohlmacher.  Such  a  condi- 
tion will  produce  an  arrest  of  development  of  the  organism 
as  a  whole,  acting  upon  the  various  organs  of  the  body, 
reducing  their  growth  and  secreting  powers.  There  are 
three  quantitative  conditions  of  the  circulation  required 
for  the  nutrition,  growth  and  functionation  of  an  organ; 
that  is  to  say,  the  minimum  amount  of  blood  will  nourish 
the  organ  and  prevent  degeneration  from  starvation,  a 
further  quantity  is  required  for  growth  and  a  still 
further  quantity  for  functionation,  consequently  any  in- 
terference in  the  quantity  of  the  blood  supply  will  first 
cause  loss  of  function,  a  further  diminution  will  arrest 
growth  and  development,  and  a  still  further  decrease  will 
cause  starvation  and  death.  Further,  the  total  quantity 
of  blood  in  circulation  will  be  materially  decreased  by  the 
narrowing  of  the  arteries. 

Other  organs  besides  the  thyroid  may  be  implicated  in 
causing  infantilism.  Imperfect  action  of  almost  any 
organ  of  the  body  can  be  conceived  as  arresting  develop- 
ment, either  physical  or  mental ;  it  has  been  described  as 


174 


THE    THYROID    AXD    PARATHYROID    GLANDS. 


occurring  in  disease  of  the  abdominal  organs,  as  the  liver 
and  pancreas,  and  especially  in  that  condition  of  lymphatic 
hypertrophy  known  as  status  lymphaticus,  in  which  the 
lymphatic  tissues  all  over  the  body  are  enlarged,  especially 
the  mesenteric  and  intestinal  glands,  a  persistent  thymus 


Fig.  61.  Fig.  62.  Fig.  63. 

Before  treatment.     After  4  months'  treatment.    After  7  months'  treatment. 
Infantilism  simulating  type  Loraine,  aged  21  years.      (Hertoghe.) 

being  also  generally  present.  Cardiac  lesions,  such  as 
mitral  stenosis,  or  insufficiency,  will  also  probably  produce 
a  defective  development  in  the  same  manner  as  congenital 
narrowing  of  the  vessels  produces  a  condition  which, 
though  simulating,  is  not  identical  with  infantilism. 
There  is  no  doubt  the  testicles  and  ovaries  have  an  effect 


INFANTILISM.  175 

upon  development,  both  physical  and  mental,  and  certain 
cases  of  infantilism  of  the  type  Loraine  are  said  to  have 
been  improved  by  the  administration  of  orchitic  extract 
when  it  was  evident  that  the  testicles  were  poorly  de- 
veloped. 

The  close  association  of  the  thyroid  with  the  physical 
and  mental  development,  as  shown  in  cretinism  and  myxe- 
dema, point  to  its  being  a  probable  primary  canse  in  the 
majority  of  cases,  the  lesions  of  the  heart,  liver,  pancreas, 
etc.,  being  secondary  to  the  general  want  of  nutrition. 

Dr.  Platauf  has  described  a  disease  under  the  name  of 
ateleiosis  (areXeiWw,  not  arriving  at  perfection),  of  which 
a  few  cases  are  on  record.  Dr.  Hastings  Gifford  has  de- 
scribed some  half  dozen  cases  as  follows :  The  most  char- 
acteristic features  of  this  disease  are  (1)  its  abrupt  onset; 
(2)  the  absence  of  perceptible  cause;  (3)  the  presence  of 
infantilism  of  a  conspicuous  kind;  (4)  the  retention  of 
unimpaired  intelligence,  and  (5)  a  special  tendency  to 
marked  delay  of  development  of  the  sexual  system.  He 
states  the  disease  may  appear  at  any  of  the  developing 
periods  of  life  and  divides  them  into  groups  according  to 
the  age  at  which  they  develop.  Group  I,  fetal  origin; 
Group  II,  early  childhood;  Group  III,  that  period  which 
intervenes  between  childhood  and  maturity,  each  present- 
ing special  aspects  depending  on  the  development  at  the 
time  of  the  onset  of  the  disease. 

Group  /.—Fetal  ateleioses  is  accompanied  by  certain  of 
the  characteristics  of  microcephaly.  There  may  be  no  ab- 
normal smallness  of  the  brain  when  compared  with  the 
size  of  the  body ;  in  fact,  the  brain  may  be  disproportion- 
ately large.  It,  therefore,  seems  as  though  the  characters 
of  microcephaly  were  due  to  the  fact  that  a  virtual  arrest 
of  the  brain  growth  takes  place  at  a  time  when  the  brain 
is  so  small  and  so  undeveloped  as  to  be  incapable  of  per- 
forming its  proper  functions.      In  only  one  of  Dr.  Gif- 


176  THE    THYKOID    AND    PAEATHYEOID    GLANDS. 

ford's  cases  was  there  imbecility  together  with  the  physi- 
ognomy which  is  characteristic  of  ateleiosis. 

Group  II. — The  disease  is  most  characteristic  when  it 
commences  in  early  childhood.  It  may  occur  in  more 
than  one  member  of  the  same  family  and  in  one  of  his 
cases  the  father  was  a  dwarf  who  had  been  exhibited.  The 
disease  resembles  cretinism  in  the  almost  complete  arrest 
of  growth  and  development.  The  form  of  the  body  re- 
mains for  the  rest  of  life  with  those  infantile  characters 
which  it  possessed  at  the  time  of  the  onset  of  the  disease. 
The  stature  is  preternaturally  short,  while  the  head  is 
large  when  compared  with  the  adult,  the  face  is  broad  and 
flat,  the  nose  sunken  at  the  bridge,  while  the  head  is  high 
when  measured  from  the  ear  to  the  vertex.  The  childlike 
form  and  physiognomy,  added  to  a  look  of  independence 
combined  with  the  wrinkling  and  weltering  of  the  skin, 
give  an  appearance  which  is  not  that  of  a  child  or  of  a 
cretin  (?),  and  is  still  less  like  that  of  an  ordinary  adult. 

In  describing  a  case  Dr.  Gilford  says  the  patient  was 
28  years  old  at  the  time  of  the  description.  He  had  ceased 
to  grow  normally  at  18  months  and  by  measurement  he 
continued  to  grow  till  his  twenty-seventh  year.  He  left 
school  at  16,  after  passing  the  sixth  standard.  "His  gen- 
eral configuration  is  that  of  a  child,  the  outlines  of  the 
muscles  are  hidden  by  fat  while  the  contour  of  both  body 
and  limbs  is  rounded  and  childish  in  appearance.  He  is 
3  feet  7-J  inches  tall,  and  his  head  19|  inches  in  circum- 
ference, and  weighs  57  pounds.  His  head  is  large,  his 
limbs  short,  and  the  relative  lengths  of  the  segments  of 
the  limbs  more  nearly  resemble  those  of  a  child  than  of 
an  adult.  His  height  is  equal  to  that  of  an  average  child 
between  6  and  7.  By  means  of  the  radiograph  the  bones 
of  the  hand  and  wrist  were  examined,  showing  ossification 
equal  to  that  of  an  average  boy  of  13.  On  the  other  hand, 
his  sexual  organs  are  no  more  developed  than  are  those  of 


INFANTILISM. 


177 


an  infant.     It  will  be  seen  that  the  rate  of  development  of 
different  parts  is  by  no  means  uniform. ' ' 

A  second  case  is  described  by  Dr.  Gifford,  as  follows : 
"He  has  the  broad,  flat  face  and  retrousse  nose  of  child- 
hood, but  combined  with  it  is  the  harsh  and  wrinkled  skin 


Fig.  64. 

Normal  boy,  17  years 

of  age. 


Fig.  65. 

Type  Loraine,  27 

years  of  age. 


Fig.  66. 

Myxedematous  Infantilism, 

18  years  of  age. 


of  middle  age.  The  countenance  is  of  the  cretinoid  type, 
but  it  differs  from  that  of  cretinism  in  that  the  lips  are  not 
thick  and  that  the  whole  face  is  lighted  up  by  a  look  of 
intelligence.  Sexual  hair  is  completely  absent  from  the 
face  as  from  every  other  part,  but  the  hair  of  the  head  is 

12 


178  THE    THYROID    AND    PARATHYROID    GLANDS. 

fairly  abundant  and  encroaches  upon  the  forehead  in  a  way 
which  is  more  often  seen  in  children  than  in  adults.  His 
muscular  strength  is  equal  to  that  of  a  child  of  his  height. 
All  the  organs  of  secretion  and  special  sense  appear  to  be 
normal.  He  sweats  on  exertion  and  is  not  particularly 
sensitive  to  cold.  His  voice  is  more  treble  than  that  of  an 
adult.  The  thyroid  gland  can  be  detected.  Dentition  is 
backward,  the  rjermanent  canines  having  apparently  not 
long  protruded  through  the  gums,  while  the  temporary 
canines  of  the  left  side  have  not  been  shed.  His  general 
health  is  excellent,  and  he  shows  no  signs  of  syphilis, 
rickets  or  of  any  other  disease."     His  age  is  not  stated. 

Dr.  Gilford  does  not  state  the  treatment,  if  any,  nor  the 
result,  but  it  seems  as  if  the  majority  of  the  symptoms 
described  in  both  cases  were  those  of  myxedema,  possibly 
associated  with  a  pathological  condition  of  some  other 
organ  which  modified  the  disease,  making  it  atypic. 

Group  III. — Ateleiosis  of  this  group  beginning  in  adult 
life  is  not  so  typical  in  physical  features  as  the  first  two 
groups.  In  these  cases  there  is  a  curious  combination  of 
the  size  and  facial  characters  of  a  boy  combined  with  the 
mannerisms  of  an  adult.  The  skin,  however,  has  not  the 
soft,  delicate  tinge  of  youth,  but  is  more  like  that  of  the 
aged  or  weather-beaten  face  of  grown-up  people.  In 
ateleiosis  there  is  at  times  a  normal  development  of  the 
sexual  organs  with  powers  of  reproduction  and  the  bones 
may  ossify  normally  at  puberty. 

The  description  of  this  group  is  meagre,  but  shows 
little  or  no  evidence  of  myxederra,  and  applies  more  to 
those  who  have  remained  childish  from  the  want  of  proper 
environment. 

Senilism  is  another  form  of  disease  often  commencing 
in  early  childhood,  which  may  be  mentioned  here  as  it  may 
possibly  be  due  to  a  hypersecretion  of  the  thyroid. 

Normal  senilism  may  occur  at  various  ages,  some  be- 


INFANTILISM.  179 

coining  senile  at  55  or  60,  others  again  being  vigorous  in 
both  mind  and  body  at  80  or  more.  This  normal  senilism 
is  due  to  the  changes  in  the  arteries  and  the  chemical 
activity  of  the  cells. 

On  the  other  hand,  precocious  development  is  an  indica- 
tion of  disease  and  a  sign  usually  of  early  decay.  Sexual 
precocity  is  probably  the  most  common  symptom,  some- 
times combined  with  rapid  growth  in  height  and  weight. 
A  well-known  case  of  great  premature  development  is  that 
of  Thomas  Hall,  known  as  the  "fat  boy  of  Willingham." 
In  his  case  there  was  a  premature  development  of  the 
sexual  organs  at  the  ninth  month ;  at  3  years  of  age  he  was 
3  feet  9  inches  tall  and  weighed  56  pounds,  and  his  muscu- 
lar strength  was  equal  to  boys  of  7  or  8  years.  His  voice 
was  "changed."  His  intelligence  was  above  the  average 
for  his  age,  while  his  sexual  organs  resembled  in  size  those 
of  a  man.  At  the  age  of  5  he  began  to  grow  a  mustache ; 
at  six  he  died  of  consumption. 

In  another  case  the  first  dentition  began  at  10  months, 
the  child  could  walk  at  12  months,  and  at  13  months  he 
was  3  feet  high  and  weighed  57  pounds,  the  head  being 
20|  inches  in  circumference.  His  mentality  was  about 
equal  to  his  years,  he  was  weak,  not  being  able  to  sit  up 
straight  without  support,  and  there  was  an  enormous 
growth  of  subcutaneous  fat;  the  skin  was  pale  and  un- 
healthy. On  close  inspection  coarse  dark  bristly  hair 
could  be  seen  sprinkled  sparsely  over  the  body  and  limbs ; 
that  on  the  upper  lip  and  on  both  sides  of  the  face  being- 
longer  than  elsewhere  and  resembling  in  quantity  that 
which  grows  at  puberty  in  normal  boys.  His  sexual  or- 
gans were  about  equal  to  those  of  a  boy  at  puberty.  He 
suffered  from  syncope  and  died  in  a  sudden  attack  at  the 
age  of  14  months. 

Progeria  is  a  form  of  senilism  which  simulates  ateleiosis, 
being  characterized  according  to  Dr.  Gilford  by  its  abrupt 


180  THE    THYEOID    AND    PAKATHYEOID    GLANDS. 

onset,  the  absence  of  perceptible  cause,  the  presence  of  a 
conspicuous  form  of  senilism,  the  retention  of  intelligence. 
Only  two  cases  appear  to  have  been  reported,  in  one  of 
which  a  postmortem  examination  showed  atheromatous 
conditions  of  the  arteries  and  the  valves  of  the  heart, 
which  would  account  for  most  of  the  symptoms. 

Yet  another  form  of  senilism  has  been  reported  by  Drs. 
A.  S.  and  T.  B.  Charcot,  in  La  Nouvelle  Iconographie  de 
la  Saltpetriere,  and  named  by  them  "  geromorphinicu- 
tanee."  The  patient  was  a  young  woman  of  20,  having 
the  appearance  of  being  60  years  of  age  owing  to  the  skin 
hanging  in  loose  folds  so  that  at  the  neck  it  hung  down 
like  the  dewlaps  of  an  ox.  In  the  other  cases  of  progeria 
reported  there  was  atrophy  of  the  hair,  nails  and  breasts, 
though  in  the  above  case  these  symptoms  were  not  present. 

Achondroplasia  is  a  form  of  arrested  development  which 
may  be  mistaken  at  first  sight  for  myxedematous  infan- 
tilism. It  was  first  described  by  Parrot  and  Depaul  in 
France  and  by  Kirchberg  and  Marchand  in  Germany,  Dr. 
Porak  writing  a  monograph  on  the  disease  in  the  Nouvelles 
arch.  d'Obst.  et  de  Gyn.,  1889-90.  In  1892  Kaufmann 
studied  three  skeletons  of  fetal  achondroplasia.  In  1893 
Thomson  reported  a  case,  Apert,  Hergott  and  Marie  other 
cases  in  1900. 

The  disease  is  usually  mistaken  for  rachitis;  the  most 
marked  traits  are  the  large  size  of  the  head  and  trunk,  the 
shortness  of  the  limbs,  the  forearm  and  the  leg  being 
longer  than  the  arm  and  thigh  respectively. 

The  symptoms  consist  of  a  macrocephalic  condition 
which  may  simulate  hydrocephalus ;  the  head  is  round,  the 
frontal  and  parietal  bones  projecting,  the  face  large,  the 
features  gross,  the  root  of  the  nose  depressed,  the  nose  en- 
larged and  rounded  at  the  end,  the  nostrils  dilated,  the 
roof  of  the  mouth  arched.  The  depression  at  the  juncture 
of  the  lumbar  vertebrae  with  the  sacrum  is  very  marked, 


INFANTILISM. 


181 


the  latter  being  elevated,  giving  the  impression  of  a  dislo- 
cation. The  hands  are  small  and  square,  reduced  in  all 
dimensions,  the  fingers  shriveled  and  of  almost  equal  di- 


Fig.  67.  Fig.  68. 

Achondroplasia.      (Comby.) 

mensions.  Sometimes  the  legs  are  bowed,  at  others  the 
knees  are  inclined  inwards.  The  muscles  are  usually  ab- 
normally developed  and  they  are  often  athletic  dwarfs. 


182  THE    THYROID    AND    PAEATHYEOID    GLANDS. 

The  genitalia  are  well  developed,  many  of  them  having 
families. 

The  bones  which  develop  directly  from  the  primitive 
embryonic  tissue,  as  the  clavicle,  ribs,  frontal  and  parietal 
bones,  etc.,  which  do  not  pass  through  the  cartilaginous 
stage,  escape  the  dystrophy,  which  explains  the  normal 
development  of  the  trunk.  On  the  other  hand,  the  ossifi- 
cation of  the  epiphyseal  cartilage  is  arrested,  the  bones  of 
the  limbs  are  unable  to  lengthen.  In  distinction  from 
rachitis,  achondroplasia  usually  commences  from  the  third 
to  the  sixth  month  of  intrauterine  life,  while  rachitis  is  a 
postnatal  disease.  In  achondroplasia  there  is  penetration 
of  the  periosteum  inward,  between  the  epiphysis  and  the 
diaphysis,  which  is  not  seen  in  cretinism  or  rachitis. 


CHAPTER   XII. 

MYXEDEMA. 

Myxedema  in  the  adult  is  usually  a  slowly  progressive 
disease,  though  cases  are  on  record  where  it  has  developed 
rapidly.  Charcot  and  Ord  report  cases  which  commenced 
with  a  chill,  in  one  case  with  hematuria,  developing  within 
a  week.  Byrom  Bramwell  states  that  in  one  of  his  cases 
the  disease  appeared  in  a  few  days  after  an  attack  of  in- 
fluenza. It  is  probable  that  in  these  cases  the  disease  had 
been  latent,  unobserved  by  the  patient  for  some  time,  until 
some  intercurrent  disease  made  a  call  upon  the  gland  for 
an  increase  of  secretion  to  which  it  was  unable  to  respond. 

The  initial  symptom  is  an  intense  lassitude  and  debility. 
Women  who  have  heretofore  been  bright  and  active  in 
their  duties  have  a  repugnance  to  exertion  both  of  body 
and  mind.  This  is  associated  with  an  increase  of  bulk  of 
the  body,  a  dryness  of  the  skin  and  an  increased  suscepti- 
bility to  cold.  I  have  observed  that  in  the  very  early 
stages  there  is  a  hyperactivity  of  the  sebaceous  glands,  the 
surface  of  the  skin  being  greasy,  while  the  head  is  full  of 
dandruff.  Frontal  headache  is  often  a  cause  of  complaint 
in  the  earliest  stages.  As  the  disease  advances  the  face, 
trunk  and  limbs  increase  in  bulk  with  the  appearance  of 
edema,  except  that  the  skin  does  not  pit  on  pressure  nor 
does  it  exude  fluid  on  puncture;  there  is  an  appearance  as 
if  the  skin  were  too  large,  hanging  in  thick  folds  on  vari- 
ous parts  of  the  body.  Ordinary  dropsy  of  the  feet  occurs 
in  about  20  per  cent  of  the  cases. 

At  the  first  glance  the  observer  notices  a  heavy,  stolid 
expression  of  sorrowful  immobility,  the  face  is  full,  broad, 
coarse  and  round,  looking  puffy  and  swollen ;  in  some  cases 

183 


184 


THE    THYB0ID    AND    PAEATHYEOID    GLANDS. 


the  wrinkles  are  flattened  out;  the  upper  eyelids  droop 
over  the  eyeballs,  causing  a  consequent  elevation  of  the 
eyebrows,  producing  transverse  wrinkles  in  the  forehead 
as  in  paralytic  ptosis.  Sometimes  the  lids  are  so  swollen 
that  they  completely  cover  the  eyeball  and  the  patient  has 
to  raise  them  with  the  finger  in  order  to  see  at  all.  The 
skin  of  the  e}^elid  has  a  peculiar  translucent  appearance. 


M^fLfc**- 

^pB 

m 

■^■r^. 

^tflc^m 

W  H|L 

,: 

f 

Fig.  69. — Myxedema. 


Baggy  swellings  appear  under  the  eyes,  which  suggest 
Bright 's  disease.  The  cheeks  are  pendulous  and  puffy. 
The  thickening  of  the  skin  usually  commences  in  the  scalp 
anterior  to  the  ears  and  in  the  nasolabial  folds.  Owing  to 
the  capillary  dilatation  there  is  often  a  rosy  tinge  over  the 
malar  bone,  abruptly  limited  by  the  lower  margin  of  the 
orbit,  contrasting  strongly  with  the  dingy  yellow  color  of 


MYXEDEMA.  185 

the  rest  of  the  face.  The  lips  are  thickened,  especially  the 
lower,  of  a  purplish  color,  feeling  firm  and  tense  to  the 
touch.  The  tongue  is  swollen,  the  gums  edematous,  bleed- 
ing easily,  the  buccal  mucous  membrane  is  also  edematous, 
sometimes  to  such  an  extent  as  to  be  injured  during  mas- 
tication. The  tonsils  are  enlarged,  the  uvula,  pharynx 
and  larynx  are  edematous.  The  swelling  of  the  soft  parts 
of  the  back  of  the  mouth  may  be  so  considerable  that  the 
patient  may  experience  difficulty  in  swallowing,  complain- 
ing of  a  choking  sensation.  The  nose  is  broad  and  coarse 
looking,  the  mucous  membranes  of  the  retronasal  cavities 
are  swollen,  impeding  respiration,  which  becomes  aggra- 
vated with  the  least  cold.  The  patient  usually  complains 
of  easily  catching  cold,  of  a  frontal  headache  and  of  a 
" stopped  up"  feeling,  such  as  is  associated  with  acute 
coryza. 

The  neck  is  usually  broad  and  thick,  with  puffy  elastic 
swellings  above  the  clavicles.  Though  the  neck  appears 
thick  the  rings  of  the  trachea  can  be  distinctly  felt  and  yet 
the  thyroid  may  not  be  palpable.  It  is,  however,  very  dif- 
ficult to  palpate  the  thyroid  gland  during  life  even  in  the 
healthy  subject,  and  it  can  be  assumed  that  if  it  can  be  so 
detected  it  has  increased  in  size. 

The  hands  are  enlarged,  thickened  and  spadelike,  the 
fingers  broad,  thickened  and  flat,  the  patient  complains 
that  they  feel  numb  and  that  they  are  unable  to  perforin 
the  finer  movements,  such  as  sewing  or  buttoning  the 
clothes;  in  some  cases  the  swelling  is  so  great  that  they 
are  unable  to  close  the  hands;  the  feet  present  the  same 
changes  and,  as  before  stated,  there  may  be  true  edema 
of  the  feet  and  ankles.  The  abdomen  is  full  and  large, 
the  trunk  as  a  whole  being  increased  in  size ;  the  vulva  and 
external  genitals  may  be  swollen. 

The  skin  is  coarse,  harsh,  rough,  dry  and  scaly  looking, 
it  may  be  split  up  into  lozenge-shaped  areas,  wrinkled  and 


186  THE    THYROID    AND    PARATHYROID    GLANDS. 

cracked,  resembling  ichthyosis.  The  sudoriferous  and 
sebaceous  glands  cease  to  secrete,  the  absence  of  sweating, 
even  in  hot  weather  or  after  muscular  exertion,  is  a  very 
characteristic  symptom.  The  electrical  resistance  of  the 
skin  is  much  increased  owing  to  its  dry  condition.  Byrom 
Bramwell  notes  the  presence  of  flat  moles  and  warts.  On 
the  abdomen  appear  patches  of  yellow  discoloration  re- 
sembling the  so-called  liver  spots;  there  is  often  a  very 
marked  desquamation,  so  much  so  that  the  scurf  can  be 
scraped  from  the  bed  linen  in  quantity.  The  hair  of  the 
scalp  has  a  tendency  to  fall  out,  complete  baldness  occa- 
sionally occurring  with  great  rapidity,  the  eyelashes 
and  eyebrows  become  thin  and  may  fall  out  entirely. 
There  is  an  incrustation  on  the  scalp,  eyebrows  and  eye- 
lids. The  fine  hairs  at  the  back  of  the  neck  fall  out  and 
give  a  peculiar  bare  appearance.  The  hair  becomes 
coarse  and  brittle  and  may  change  color.  In  the  axillse 
and  the  pubes  the  hair  falls  out,  the  parts  may  become 
quite  bare. 

The  nails  are  brittle,  dry  and  opaque,  the  teeth  carious 
and  loose ;  in  many  cases  there  is  an  increased  secretion  of 
saliva  which  may  be  very  troublesome.  It  has  been  ob- 
served that  the  secretion  from  the  parotid  gland  in  these 
cases  contains  an  excess  of  mucus.  There  is  also  a  run- 
ning from  the  eyes  and  nose. 

The  mucous  membranes  of  the  stomach,  intestines  and 
rectum  share  in  the  general  tumefaction  of  the  mucous 
membranes,  producing  malnutrition  and  the  obstinate  con- 
stipation from  which  the  patients  invariably  suffer.  The 
stomach  examination  after  the  Salzer-Ewald  testmeal 
shows  a  marked  hypochlorhydria,  sometimes  anachlorhy- 
dria,  usually  with  excess  of  organic  acid,  also  excess  of 
mucus,  want  of  motility  and  of  absorption. 

There  is  a  wheezing  inspiration  in  advanced  cases  which 
is  often  ascribed  to  asthma,  the  patient  may  make  a  noisy 


MYXEDEMA.  187 

gasping  inspiration  after  a  sentence.  From  the  edematous 
condition  of  the  nasal  nracous  membrane  the  patients  are 
compelled  to  breathe  through  the  mouth,  consequently 
their  intonation  is  harsh,  rasping  and  nasal ;  when  adenoid 
growths  are  present,  which  is  often  the  case,  the  breathing 
is  noisy  even  at  rest.  Owing  to  the  thickening  of  the 
vocal  cords  and  the  enlargement  of  the  tongue  the  speech 
has  a  peculiar  sound  as  if  the  patient  had  something  in 
her  mouth.  Owing  to  the  impaired  mentality  the  speech 
is  slow  and  deliberate. 

The  mental  condition  is  always  abnormal,  resembling 
dementia;  there  is  a  lack  of  quickness  of  perception,  a 
slowness  of  thought,  an  emotional  depression  and  suppres- 
sion combined  with  listlessness  and  torpor ;  the  repugnance 
to  exertion  of  any  kind  is  a  marked  feature  and  is  often 
the  first  symptom  noticed  by  the  patient.  Hallucinations 
of  sight  and  hearing  are  not  uncommon ;  there  may  be  a 
singing  in  the  ears  and  even  ' '  hearing  voices. ' '  The  hallu- 
cinations of  sight  resemble  those  of  alcoholism ;  less  often 
hallucinations  of  taste  and  smell  occur,  any  of  which  may 
be  so  severe  as  to  prevent  the  patient  from  sleeping ;  as  a 
rule,  however,  patients  sleep  well  or  excessively.  Some 
few  are  garrulous,  continuing  to  talk  regardless  of  ques- 
tions or  interruptions,  simulating  mania.  Usually  these 
patients  are  even  tempered,  but  sometimes  very  irritable, 
having  violent  fits  of  passion;  others  are  suspicious  of 
their  friends  and  of  themselves.  The  memory  is  much 
impaired.  The  placidity  and  stolidity  of  myxedema  is  in 
marked  contrast  to  the  excitability  and  perpetual  unrest 
of  Basedow's  disease.  The  mental  symptoms  may  become 
so  severe  as  to  be  insanity,  rarely  maniacal.  They  are 
usually  melancholic. 

The  tactile  sensibility  of  the  skin  is  delayed  or  dimin- 
ished, sight  and  hearing  impaired.  Headache,  cramps, 
neuralgic  pains,  faintness,  giddiness,  tinnitus  aurium  and 
muscular  pains  are  often  accompanying  symptoms. 


188  THE    THYROID    AND    PAEATHYEOID    GLANDS. 

The  gait  is  heavy  and  clumsy,  the  muscular  power  is 
much  impaired  and  there  is  a  certain  amount  of  loss  of 
coordination,  the  patient  being  apt  to  stagger  and  even  to 
fall.  The  walk,  owing  to  the  increased  size  of  the  body 
and  the  muscular  weakness,  combined  with  the  slowness 
and  numbness  of  the  movements,  has  been  termed  the 
' '  hippopotamus  gait. ' ' 

The  reflexes  are  usually  diminished,  the  knee  jerks  often 
abolished.  The  sensibility  is  often  especially  impaired  in 
regard  to  heat  and  cold,  the  patients  being  extremely  sus- 
ceptible to  variations  in  external  temperature,  complaining 
of  feeling  cold.  It  has  been  observed  by  Horsley  and 
others  that  thyroidectomized  animals  would  survive  the 
operation  much  longer  and  symptoms  even  not  developed 
at  all  as  long  as  the  subject  was  kept  in  a  room  at  a  high 
temperature.  The  patients  often  complain  of  a  tingling  or 
pricking  sensation  of  the  skin.  The  body  temperature  is 
subnormal,  being  96.5  degrees  F.  or  even  a  little  lower. 
The  subnormal  temperature  and  the  susceptibility  to  cold 
are  due  to  decreased  oxidation  and  a  pathologic  condition 
of  the  cutaneous  capillary  system. 

The  pulse  is  slower  than  normal,  soft  and  weak,  the 
heart's  action  feeble,  the  second  sound  accentuated,  the 
mean  blood  pressure  increased,  the  heart  dilated,  the  car- 
diac muscle  degenerated  and  the  arteries  atheromatous; 
in  the  latter  case  thyroid  feeding  must  be  conducted  with 
caution.  Fainting  may  occur,  palpitation  is  often  com- 
plained of  after  exertion.  Anemia  is  usually  present,  the 
hemoglobin  may  be  as  low  as  60  per  cent  and  the  red 
corpuscles  reduced  to  3,000,000. 

The  appetite  is  poor,  as  is  the  digestion;  obstinate  con- 
stipation is  the  rule,  diarrhea  the  exception,  but  as  is  com- 
mon in  hypochlorhydria,  there  are  often  severe  attacks  of 
diarrhea  without  apparent  cause. 

In  females  amenorrhea  is  the  rule,  menorrhagia  the  ex- 


INCOMPLETE    MYXEDEMA    IN    ADULT.  180 

ception.  In  cases  of  amenorrhea  there  may  be  occasional 
profuse  hemorrhages ;  there  is  also  a  marked  tendency  to 
hemorrhage  owing  to  the  high  mean  pressure  and  disease 
of  the  vessels  as  well  as  to  the  reduced  coagulability  of 
the  blood.  Epistaxis  and  bleeding  from  the  gums  are 
common,  any  small  injury  may  bleed  profusely.  Should 
a  case  become  pregnant,  which  rarely  happens,  postpartem 
hemorrhage  should  be  guarded  against. 

The  urine  is  usually  normal  or  increased  in  quantity, 
the  specific  gravity  low,  total  nitrogen  low,  urea  nitrogen 
decreased,  ammonia  nitrogen  increased,  uric  acid  nitrogen 
decreased  or  normal,  and  the  residual  nitrogen  increased. 
The  carbon  nitrogen  factor  is  high,  the  carbon  elimination 
being  greater  than  the  nitrogen;  oxalic  acid  is  often  in- 
creased, total  sulphates  are  low,  ethereal  sulphates  high 
and  the  neutral  sulphur  very  high.  Indican  is  excessive, 
bile  pigment  and  indoxylglycuronic  acid  are  often  present, 
the  latter  sometimes  in  sufficient  quantity  to  reduce  Fail- 
ing's solution.  Albumin  is  sometimes  present,  and  albu- 
mose.  Byrom  Bramwell  reports  a  case  where  serum 
globulin  was  present  but  no  serum  albumin.  It  would 
have  been  interesting  in  this  case  to  have  had  an  analysis 
of  the  blood,  in  order  to  have  observed  the  proportion  of 
serum  albumin  and  serum  globulin.  I  have  found  nucleo- 
albumin  in  several  cases,  but  rarely  serum  globulin  or 
serum  albumin,  except  in  cases  where  there  was  evidently 
an  associated  kidney  lesion. 

INCOMPLETE    MYXEDEMA   IN    THE    ADULT. 

Between  the  healthy  condition  of  the  gland  and  its  com- 
plete or  almost  complete  cessation  of  function  there  are 
necessarily  an  infinite  number  of  degrees  producing  vary- 
ing symptoms,  more  or  less  acute,  giving  varied  clinical 
pictures,  which  it  is  of  importance  to  recognize  as  pointing 
to  possible  relief  by  thyroid  feeding.     In  the  cases  where 


190  THE    THYROID   AND    PAEATHYEOID    GLANDS. 

there  is  a  hypothyroidea,  either  congenital  or  acquired,  a 
condition  of  premature  senility  is  produced,  the  patient 
appears  old  for  her  years,  she  becomes  gray  early,  either 
generally  or  in  patches,  the  hair  may  fall  out  rapidly  either 
over  the  temples  in  front,  along  the  median  line  or  at  the 
back  of  the  head,  the  down  on  the  back  of  the  neck  disap- 
pears and  there  is  a  baldness  extending  up  to  the  occipital 
protuberance,  where  it  looks  scanty  and  ragged,  the  skin  is 
yellow,  shriveled  and  coarse,  the  hair  feels  brittle  and  dry 
and  is  fluffy,  looking  untidy;  there  is  an  incrustation  of 
the  scalp  or  there  may  be  a  large  quantity  of  dandruff, 
sometimes  there  are  bald  patches.  These  changes  are 
often  concealed  by  the  barber 's  art  and  must  be  especially 
looked  for.  The  eyebrows  and  eyelashes  are  thin  or  may 
be  entirely  absent;  there  is  a  scaly  condition  of  the  skin 
at  the  external  angles  of  the  eyebrows,  often  accompanied 
with  itching.  The  teeth  are  generally  decayed,  especially 
the  molars ;  the  gums  are  inflamed  and  soft,  bleeding 
easily;  the  teeth  are  covered  with  black  or  green  tartar, 
rarely  yellow,  especially  the  incisors  of  the  lower  jaw. 
The  tongue  is  swollen  and  indented  with  the  teeth.  The 
nasal  accumulation  of  tartar  forces  back  the  gums,  the 
teeth  become  loose  and  fall  out.  The  tonsils  are  swollen, 
often  hypertrophied.  The  mucous  membrane  of  the 
pharynx  is  red  and  edematous,  adenoids  are  often  present. 
The  fossae  are  contracted,  being  obstructed  by  the  swollen 
mucous  membrane ;  adenoids  are  common ;  sometimes  in 
mild  cases  the  nasal  fossae  are  normal  except  during  men- 
struation or  a  slight  cold,  when  the  posterior  portions 
become  engorged ;  the  nasal  condition  causes  the  patient  a 
great  deal  of  inconvenience,  and  is  generally  attributed  to 
a  chronic  catarrh  to  which  the  patient  ascribes  her  mental 
heaviness  and  drowsiness.  Sometimes  the  condition  pro- 
duces continued  sneezing.  The  voice  is  high  pitched  and 
leathery,  usually  being  more  discordant  during  menstrua- 
tion and  pregnancy. 


INCOMPLETE    MYXEDEMA    IN    ADULT.  191 

The  headaches  which  are  often  attributed  to  cerebral 
anemia  are  of  two  kinds,  sometimes  appearing  in  the 
frontal  sinus  or  behind  the  orbits,  as  in  acute  coryza,  or 
they  may  appear  in  the  occipital  region.  They  are  often 
described  as  migraine,  but  they  differ  from  true  migraine 
in  being  at  their  worst  in  the  morning,  disappearing  as  the 
day  wears  on  or  after  a  full  meal.  The  patient  is  so  accus- 
tomed to  this  that  she  may  not  complain  of  it  till  her  atten- 
tion is  called  to  it ;  she  usually  attributes  the  falling  out  of 
the  hair  or  its  turning  gray  to  these  headaches,  or  again 
she  may  account  for  the  headaches  by  the  condition  of  her 
teeth.  The  thickening  of  the  skin,  which  is  so  marked  a 
symptom  in  complete  myxedema,  is  not  present,  or  only 
very  slightly ;  there  may  be  a  pufhness  under  the  eyes,  a 
red  patch  on  the  cheek  extending  to  the  nose ;  the  skin  has 
a  dirty  yellow  color  or  it  may  have  a  clear  waxy  appear- 
ance ;  the  raised  eyebrows  and  transverse  wrinkles  of  the 
brow  may  also  be  present ;  the  whole  expression  is  one  of 
sorrowful  fatigue.  Murray,  in  the  Brit.  Med.  Jour.,  1898, 
describes  cases  which  he  calls  ' '  early  thyroidal  fibrosis, ' '  in 
which  he  has  observed  hallucinations  of  sight  and  hearing, 
the  patients  seeing  objects  indistinctly  defined  resembling 
cats,  mice,  rats,  etc.,  which  rapidly  traverse  the  room  when 
it  is  well  lighted.  Buzzing  and  ringing  in  the  ears  is  com- 
mon and  may  go  so  far  as  to  take  the  distinct  sound  of  bells. 
Hertoghe  has  made  the  same  observation. 

There  is  also  a  rachialgia  with  pain  between  the  should- 
ers the  patient  suffering  from  insomnia,  falling  into  a 
sound  sleep  in  the  early  hours  of  the  morning,  but  is 
shortly  awakened  with  pains  which  she  describes  as  though 
the  back  were  being  wrenched  asunder,  so  intense  is  the 
discomfort  that  sleepy  and  tired  though  the  patient  feels, 
she  is  unable  to  remain  in  bed  and  rises  tired  and  unre- 
f  reshed,  with  a  headache  and  rachialgic  pains,  which,  how- 
ever, become  less,  disappearing  entirely  as  the  day  ad- 


192 


THE    THYROID    AND    PARATHYBOID    GLANDS. 


varices  only  to  appear  again  on  the  following  morning. 
Often  the  joints  and  muscles  are  painful,  usually  attrib- 
uted to  rheumatism,  but  the  temperature  is  normal  or  sub- 
normal and  the  pains  do  not  yield  to  rheumatic  treatment ; 
as  the  case  advances  the  pains  may  appear  first  in  one 
part  and  then  in  another,  or  in  several  places  at  once.  The 
patient  often  complains  of  chills,  which  may  occur  with 
great  regularity  at  a  given  time  of  the  day,  usually  be- 


Fig.  70.— Before  treatment.  Fig.   71. — After  6  months'  treatment. 

Incomplete  Myxedema. 

tween  4  and  6  o'clock;  they  simulate  malaria,  but  the 
Plasmodia  are  not  present  nor  do  they  yield  to  quinin. 
The  patient  complains  of  feeling  cold  in  spite  of  coverings 
and  wraps,  the  feet  and  hands  being  especially  susceptible. 
A  shortness  of  breath  is  a  very  constant  symptom,  some- 
times very  slight  and  only  noticeable  on  muscular  exertion 
or  going  upstairs;  at  times  it  is  accentuated.  Occasion- 
ally, in  advanced  cases,  the  patient  makes  a  quick,  short 
noisy  inspiration  after  each  sentence,  usually  ascribed  to 
asthma  or  embonpoint.  This  oppression  exists  even  when 
the  patient  is  not  stout,  and  on  careful  examination  of  the 


INCOMPLETE    MYXEDEMA    IX    ADULT.  193 

chest  dilatation  of  the  base  of  the  thorax  will  be  found. 
Pulmonary  emphysema  is  often  difficult  to  explain  and 
may  be  looked  upon  as  pulmonary  senility ;  as  hypothyroi- 
dea  produces  premature  senility,  emphysema  is  the  senile 
change  in  the  lung  corresponding  to  the  graying  of  the 
hair.  The  oppression  of  respiration  is  often  accompanied 
by  palpitation  and  lancinating  pains  over  the  region  of  the 


Fig.  72.— Before  treatment.  Fig.  73.— After  10  months' treatment. 

Incomplete  Myxedema. 

heart,  resembling  angina  pectoris.  There  is  often  dilata- 
tion of  the  left  heart  and  aortic  insufficiency,  the  result  of 
the  increased  mean  blood  pressure  from  the  contraction  of 
the  arterioles  and  capillaries  of  the  skin. 

The  venous  system  suffers  from  the  premature  senility, 
varices,  varicoceles  and  hemorrhoids  are  common,  the 
veins  in  the  back  of  the  hands  are  dilated,  even  in  the 
young  and  sometimes  on  the  anterior  surface  of  the  thorax. 
The  capillary  system  suffers  with  the  rest  of  the  vessels, 
as  shown  by  the  dry,  harsh  desquamatory  condition  of  the 
skin ;  the  red  patches  on  the  cheeks,  the  condition  of  the 

13 


194  THE    THYROID    AND    PAEATHYEOID    GLANDS. 

gums  and  mucous  membranes.  Of  the  changes  in  the 
arterial  system  the  loss  of  tonicity  is  the  most  marked. 

The  liver  often  becomes  congested.  Ver  Ecker  has 
shown  that  thyroidectomized  animals  have  a  marked  con- 
gestion of  the  liver ;  Berkeley  observed  a  general  passive 
congestion  of  the  organs  in  mice  poisoned  by  thyroid  feed- 
ing. In  mild  cases  the  liver  is  simply  enlarged,  in  more 
advanced  cases  the  patients  complain  of  a  weight  in  the 
hepatic  region ;  there  is  also  pain  over  the  gall  bladder  and 
gall  stones  are  frequently  present. 

The  symptom  which  seems  to  predominate  in  all  cases 
of  hypothyroidea,  whether  in  cretinism,  myxedema  or  in 
the  incomplete  forms,  is  obstinate  constipation ;  to  this  the 
patient  often  ascribes  all  her  ailments. 

Amenorrhea  and  dysmenorrhea  are  the  rule;  there  is 
also  retroflexion  of  the  uterus  even  in  the  young,  due  to 
imperfect  development  of  the  posterior  wall  of  the  uterus, 
fibromas  are  often  present,  to  the  retroflexion  and  the 
fibromas  the  gynecologist  ascribes  all  the  symptoms,  but 
operation  fails  to  relieve  the  patient.  Impotence  and  loss 
of  sexual  desire  are  a  common  cause  of  patients  seeking 
advice. 

Owing  to  the  increased  activity  of  the  gland  during 
pregnancy  the  patient  is  often  in  better  health  during  this 
period,  the  extra  secretion  being  utilized  by  the  maternal 
system,  often  to  the  detriment  of  the  fetus.  During  this 
period  many  of  the  symptoms  disappear  entirely  and  the 
patient  becomes  normal,  but  at  the  end  of  lactation  she 
relapses  and  is  generally  worse  than  before.  The  first 
symptoms  may  appear  after  one  or  more  pregnancies,  if 
the  patient's  bowels  have  been  regular  before  and  become 
constipated  after  pregnancy,  or  if  the  menstruation  be- 
comes abnormal ;  it  is  well  to  look  further  for  evidence  of 
hypothyroidea,  especially  should  the  patient  who  pre- 
viously was  active  and  energetic  become  languid  and 
apathetic  regarding  her  household  duties. 


INCOMPLETE    MYXEDEMA    IN    ADULT.  195 

"When  the  disease  is  fairly  advanced  the  patients  become 
somnolent,  fatigued,  languid  and  apathetic,  everything  to 
be  done  appears  to  be  above  their  physical  and  moral 
strength.     They  complain  of  feeling  unnatural. 

The  heart 's  action  is  feeble  and  the  second  sound  accen- 
tuated, or  there  may  be  aortic  valvular  insufficiency,  the 
pulse  is  slower  than  normal  and  the  temperature  may  be 
subnormal;  there  is  often  a  feeling  of  depression,  which 
appears  to  the  patient  to  emanate  from  the  cardiac  region. 
The  erythrocytes  are  decreased  as  is  the  hemoglobin. 
There  is  often  a  tendency  to  hemorrhage,  slight  injuries 
bleeding  freely,  epitaxis  may  occur  and  postpartem  hem- 
orrhage has  to  be  guarded  against.  These  latter  symp- 
toms are  due  to  the  increased  blood  pressure  and  the  re- 
duced coagulability  of  the  blood.  In  the  urine  there  may 
be  albumin  and  casts  due  to  the  venous  congestion  of  the 
kidneys.  I  have  rarely  found  kidney  insufficiency  in  these 
cases,  the  freezing  point  of  the  urine  being  within  normal 
limits,  serum  albumin  and  serum  globulin  are  rare  though 
nucleoalbumin  is  not  uncommon.  The  nitrogen  elimina- 
tion is  low.  Byrom  Bramwell  has  noted  large  quantities 
of  mucus  in  some  of  his  cases.  In  the  urine  oxalic  acid  is 
often  in  excess,  phosphoric  acid  is  low,  neutral  sulphur  is 
high,  being  often  25  per  cent  of  the  total  sulphur.  Chlo- 
rids  are  high  in  proportion  to  the  nitrogen.  There  is  an 
excess  of  ethereal  sulphates,  indican  and  skatoxyl  being 
in  excess,  due  to  the  constipation.  The  proportions  of 
the  nitrogen  eliminated  are  pathologic,  the  urea  nitrogen 
may  be  as  low  as  65  per  cent  of  the  total  nitrogen,  am- 
monia nitrogen  6  to  7  per  cent  or  even  higher.  The  uric 
acid  nitrogen  low  or  normal,  the  residual  nitrogen  is  often 
very  high.  The  carbon  nitrogen  factor  is  usually  high; 
urorosein  is  in  excess,  bile  pigments  present  in  traces  and 
sometimes  indoxylglycuronic  acid. 

The  stomach  usually  shows  a  hypo-  or  anachlorhydria. 


196  THE    THYROID    AND    PARATHYROID    GLANDS. 

The  latter  is  rare ;  there  is  an  excess  of  mucus  and  organic 
acids. 

There  are  also  certain  mental  changes  which  may 
amount  to  insanity,  sometimes  melancholic,  at  other  times 
maniacal  or  simply  delusional.  These  cases  will  be  con- 
sidered later. 

The  multiplicity  and  complexity  of  the  symptomatic  pic- 
ture calls  for  the  most  careful  examination  by  the  physi- 
cian, and  even  then  he  is  often  compelled  to  make  a  diag- 
nosis by  exclusion. 

Treatment. — The  treatment  of  all  forms  of  myxedema  is 
the  same,  viz :  the  administration  of  the  thyroid  gland  of 
some  animal,  that  of  the  sheep  usually  being  employed. 

Since  the  discovery  of  Murray,  in  1891,  that  myxedema 
could  be  successfully  treated  by  subcutaneous  injections  of 
an  extract  of  the  thyroid  gland  of  the  sheep,  and  the 
further  advance  of  Howitz,  of  Copenhagen,  and  Mackenzie 
and  Fox,  in  1892,  that  the  administration  of  the  thyroid 
by  the  mouth  was  equally  efficacious  the  disease  is  no 
longer  looked  upon  as  beyond  relief.  If  the  patient  is  suf- 
fering from  abolition  of  function  of  the  thyroid  gland 
alone  with  no  complications  thyroid  feeding  is  a  specific, 
and  no  case  will  fail  to  be  improved  or  cured  by  its  use. 
There  are  cases  which  apparently  do  not  react  to  thyroid 
treatment  in  which  there  is  some  complicating  disease,  or 
the  disease  has  produced  a  dementia  from  which  there  is 
no  recovery.  In  other  cases  the  treatment  fails  from  the 
nonabsorption  of  the  drug.  The  active  principle  of  the 
gland  is  not  absorbed  from  the  stomach,  it  being  only 
soluble  in  alkaline  solutions  and  is  precipitated  by  organic 
and  inorganic  acids.  Should  the  intestinal  tract  of  the 
patient  be  acid  throughout  its  whole  length,  a  condition 
which  must  be  not  uncommon  in  these  cases,  with  whom 
obstinate  constipation  and  intestinal  putrefaction,  pro- 
ducing fatty  acids  in  quantity,  is  a  constant  condition, 


INCOMPLETE    MYXEDEMA    IN    ADULT.  197 

there  would  be  no  absorption  of  the  drug.  It  is,  therefore, 
necessary  that  in  all  cases  attention  should  be  paid  to  the 
condition  of  the  digestive  tract.  The  administration  of 
natrium  bicarbonate  in  five  or  ten  grain  doses  and  two  or 
three  grains  natrium  sulphate  in  a  tumbler  of  water  about 
thirty  minutes  before  meals  washes  out  the  stomach,  neu- 
tralizes the  fatty  acids  and  helps  to  relieve  the  constipa- 
tion, the  sulphuric  acid  of  the  sulphate  combining  with  the 
phenols  formed  in  the  colon,  rendering  them  innocuous. 
The  desiccated  thyroid  gland,  preferably  that  manufac- 
tured by  Armour  &  Co.,  should  be  given  in  one  grain  doses 
three  times  a  day  and  gradually  increased  to  three  grains ; 
it  is  rarely  advisable  to  go  above  this  dose,  though  occa- 
sionally five  grains  is  borne  without  producing  symptoms 
of  thyroidismus.  It  should  always  be  administered  with 
caution,  especially  in  those  cases  where  the  heart  is  weak, 
or  the  arteries  degenerated,  and  it  should  be  withdrawn  on 
the  first  symptoms  of  thyroidismus,  commencing  again  in 
a  few  days  with  a  smaller  dose. 

The  addition  of  a  little  strychnia  and  arsenious  acid 
have  a  decidedly  beneficial  effect.  For  the  constipation 
there  is  nothing  equal  to  sodium  glycocholate  mass  and 
magnesium  oxid.  From  three  to  five  grains  of  each  will, 
after  a  week  or  two,  make  the  bowels  act  regularly. 

Where  the  mental  depression  is  severe  the  addition  of 
one  grain  of  opium  to  each  dose  of  the  thyroid  will  act  as 
a  heart  stimulant. 

In  children  the  dose  should  never  exceed  two  grains  a 
day  to  commence  with,  and  it  is  better  to  begin  with  one, 
gradually  increasing  it  according  to  how  it  is  borne.  In 
children  the  alkali  treatment  is  of  as  much  or  more  impor- 
tance than  in  the  adult ;  strychnia  and  arsenic  are  useful 
adjuncts  in  children  but  the  use  of  opium  requires  caution. 
The  glycocholate  of  soda  and  magnesium  oxid  are  not 
adapted  for  children  unless  they  can  swallow  a  capsule ;  the 


198  THE    THYROID    AND    PABATHTKOID    GLAXDS. 

taste  of  the  glycocliolate  is  too  nauseous  to  be  adminis- 
tered in  solution;  liquorice  will  disguise  the  taste  fairly 
well. 

Should  there  be  dilatation  of  the  heart  or  if  the  skin 
symptoms  are  severe,  the  Shott  baths  are  a  very  useful 
adjunct;  when  given  at  night  they  produce  refreshing  and 
prolonged  sleep. 

The  diet  should  be  plain  and  substantial,  calculated  to 
assist  in  relieving  the  constipation. 


CHAPTER   XIII. 
BASEDOW'S    DISEASE. 

Basedow's  disease,  exophthalmic  goitre,  or  Graves'  dis- 
ease is  one  of  the  most  interesting  of  diseases  on  account 
of  the  peculiarity  of  its  symptoms  and  the  mystery  of  its 
etiology  and  pathology.  It  was  first  described  in  1835  by 
the  celebrated  Dublin  physician  Graves,  and  in  1840  Base- 
dow gave  a  complete  and  elaborate  account  of  its  clinical 
features.  Since  that  date  the  literature  on  the  subject  has 
reached  enormous  proportions,  as  can  be  gathered  from 
Albert  Kocher's  monograph  on  the  surgical  treatment  of 
the  disease,  which  contains  no  less  than  1423  references. 

Basedow's  disease,  like  myxedema,  is  much  more  com- 
mon in  women  than  in  men,  the  proportions  varying  from 
5  to  10  to  1  according  to  different  authors  and  the  age 
from  14  to  60  years,  with  the  majority  of  cases  between 
20  and  40.  Unlike  myxedema  marriage  and  childbearing 
seem  to  have  little  effect  in  this  disease,  the  preponderance 
of  cases  occurring  in  married  women,  though  Byrom 
Bramwell,  in  his  list  of  79  cases,  found  47  were  single  and 
26  were  married  or  widows. 

Direct  heredity,  viz:  that  the  parents  had  Basedow's 
disease  and  that  it  descended  directly  to  the  offspring  has, 
so  far  as  I  can  find,  never  been  observed;  occasionally 
more  than  one  member  of  a  family  is  affected.  There  are 
many  cases  recorded  where  the  parents  or  near  relatives 
have  been  affected  with  some  other  form  of  nervous  dis- 
ease, or  that  there  is  some  history  of  general  nervousness, 
hysteria,  epilepsy  or  insanity  in  some  more  or  less  remote 
relation.  The  weakness  of  the  argument  in  favor  of 
heredity  in  this  and  many  other  diseases,  is  shown  by  the 

199 


200 


THE    THYROID    AND    PARATHYROID    GLANDS. 


list  of  cases  which  Byrorn  Bramwell  cites  as  evidence  of 
the  heredity  of  the  disease ;  out  of  79  cases  he  finds  that  in 
one  case  a  sister  had  a  large  goitre,  in  one  case  an  aunt 
had  Basedow's  disease,  in  one  case  a  cousin,  two  cases 
were  sisters,  and  in  another  case  the  patients  were  sisters. 
In  these  six  cases  out  of  a  total  of  79  only  one  case  can  be 


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tttaMf          '    aC*"«r 

KM 

m 

w^-     f^Kt 

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Fig.  74. —  Basedow's  disease. 

attributed  to  heredity  and  that  was  from  an  aunt.  Ex- 
haustion from  acute  illness,  especially  influenza  or  loss  of 
blood,  seems  to  be  an  exciting  cause.  Peripheral  irrita- 
tion in  the  nose  and  in  the  abdominal  and  especially  pelvic 
viscera  is  also  an  exciting  cause ;  many  cases  are  on  record 
where  ovarian  or  uterine  troubles  were  associated  with 
symptoms  of  Basedow's  disease,  and  that  after  laparot- 
omy the  symptoms  disappeared,  which  may  be  accounted 


Basedow's  disease.  201 

for  by  the  connection  of  the  thyroid  with  the  organs  of 
generation.  Anemia  seems  to  play  a  part  in  the  causation 
of  the  disease.  Nervous  shock,  profound  mental  anxiety 
and  fright  seem  to  have  some  effect  upon  its  causation, 
though  rnore'often  a  symptom  rather  than  a  cause.  Many 
of  the  symptoms  and  the  facial  expression  are  identical 
with  those  of  fright. 

The  etiology  of  Basedow's  disease  is  as  yet  unsettled. 
Though  many  theories  have  been  brought  forward  at  vari- 
ous times  by  different  observers  none  have  received  gen- 
eral acceptance.  Basedow  considered  that  the  disease  was 
the  result  of  a  primary  change  in  the  blood,  but  recent 
investigators  have  shown  that  the  red  corpuscles  and  the 
hemoglobin  are  usually  normal  in  amount  and  when 
anemia  occurs  it  is  due  to  starvation  from  continued 
vomiting.  Stokes  was  of  opinion  that  the  cause  of  the 
disease  was  a  heart  lesion.  Lemke  attributed  it  to  a 
disease  of  the  muscle  of  the  heart  and  Askanazy  found 
histological  changes  in  the  muscle  tissue  in  many  cases. 
Jakob  claims  that  these  muscle  changes  are  of  toxic  origin 
but  it  is  more  probable  they  are  due  to  an  abnormal  meta- 
bolic condition.  Disease  of  the  pelvic  viscera  has  from 
time  to  time  been  observed  associated  with  this  disease, 
the  symptoms  disappearing  after  operation  on  the  pelvic 
lesion.  Enteroptosis,  diseases  of  the  nose,  floating  kid- 
ney and  autointoxication  have  all  had  their  advocates. 
Eenaut  described  the  cirrhosis  of  the  thyroid  gland  and 
claimed  that  an  imperfect  lymph  circulation  was  the  cause, 
which  was  supported  by  Miiller,  who  pointed  out  that  the 
lymph  glands  of  the  neck  are  swollen;  presumably  the 
thyroid  was  unable  to  eliminate  its  colloid  into  the  lym- 
phatics, which  would  cause  swelling  of  the  gland,  with  pos- 
sibly a  change  in  the  colloid  substance  and  also  necessi- 
tate its  elimination  into  the  blood  vessels.  Charcot  and 
Baschan  claimed  that  the  disease  was  primarily  due  to 


202  THE    THYROID   AND    PARATHYROID    GLAXDS. 

alterations  in  the  ganglion  cells  of  the  cortex.  Ballet  con- 
siders the  disease  as  a  bulbar  neurosis  and  von  Cyon  as  a 
lesion  of  the  depressor  cordis. 

Several  writers  agree  that  the  symptoms  are  the  result 
of  an  irritative  lesion  of  the  sympathetic.  Pathologists, 
however,  have  been  unable  to  find  any  constant  lesion  in 
the  ganglia  either  of  the  neck,  thorax  or  abdomen.  There 
being  no  marked  or  constant  dilatation  of  the  pupils 
argues  against  the  disease  being  of  sympathetic  origin ;  on 
the  other  hand,  the  dilatation  of  the  blood  vessels,  which  is 
a  constant  condition,  may  very  well  be  due  either  to  a 
paralysis  of  the  vasoconstrictor  or  irritation  of  the  vaso- 
dilator fibres  of  the  sympathetic.  Pressure  on  the  sympa- 
thetic of  the  neck  by  the  enlarged  gland  is  also  said  to 
cause  the  disease,  and  some  cases  have  recovered  after 
section  of  the  sympathetic  of  the  neck.  Frederick  sug- 
gested that  there  might  be  a  paralysis  of  the  vasomotor 
nerves  which  would  cause  a  dilatation  of  the  coronary 
arteries,  thereby  increasing  the  excitability  of  the  cardiac 
ganglia  causing  increased  action  of  the  heart.  Lesions  in 
the  nuclei  of  the  pneumogastric  nerve  and  other  structures 
in  the  medulla  oblongata  have  been  found  but  nothing 
that  was  not  probably  secondary  in  its  origin.  E.  Ze- 
deschi  implicates  the  restiform  bodies.  He  states  that 
lesions  of  the  anterior  portion  of  the  restiform  bodies  in 
animals  produce  marked  symptoms  of  Basedow 's  disease ; 
further  that  animals  in  whom  the  symptoms  of  Basedow 's 
disease  have  been  induced  by  lesions  of  the  restiform 
bodies  and  when  such  symptoms  have  been  diminished  or 
have  disappeared  they  may  be  reproduced  wholly  or  in 
part  by  feeding  with  thyroid  to  the  point  of  hyperttiyroid- 
ism.  He  further  states  that  lesions  of  the  restiform  bodies 
in  thyroidectomized  animals  do  not  cause  symptoms  of 
Basedow's  disease.  In  animals  in  whom  the  symptoms 
of  Basedow's  disease  have  been  induced  through  lesions 


Basedow's  disease.  203 

of  the  restiform  bodies  removal  of  the  thyroid  diminishes 
or  causes  the  disappearance  of  the  greater  part  of  snch 
symptoms.  These  latter  experiments,  if  confirmed,  are 
of  great  importance. 

Mobius  has  strongly  advocated  the  theory  that  the 
primary  cause  of  the  disease  is  hypertrophy  and  hyper- 
secretion of  the  thyroid  gland.  Greenfield  and  George 
Murray  support  this  view,  the  latter  arguing  that  the 
gland  in  Basedow 's  disease  is  to  be  compared  to  the  mam- 
mary gland  during  lactation.  The  enlargement  of  the 
thyroid  is  one  of  the  chief  symptoms  and  even  when  com- 
paratively slight  there  is  an  increased  circulation  through 
the  gland,  producing  a  hypersecretion  which  must  neces- 
sarily find  its  way  into  the  circulation.  Many  of  the 
symptoms  of  Basedow's  disease  are  the  exact  opposite  of 
those  of  myxedema,  which  is  admittedly  the  result  of 
absence  of  thyroid  secretion ;  further,  it  has  been  observed 
that  Basedow's  disease  may  develop  into  myxedema  on 
the  subsidence  of  the  swelling,  due  to  atrophy  of  the 
gland;  while  the  converse,  viz:  myxedema  developing 
into  Basedow's  disease  has  never  been  recorded  and  more 
conclusive  still  is  the  fact  that  partial  excision  of  the 
enlarged  gland  has  often  been  followed  by  improvement 
and  cure  of  the  disease.  Edmunds  has  produced  exoph- 
thalmos, tumor,  etc.,  by  feeding  thyroid  to  monkeys,  and 
cases  are  on  record  where  the  symptoms  have  developed 
in  man  from  overdosing  with  thyroid  extract. 

In  the  following  table  the  symptoms  of  myxedema, 
Basedow 's  disease  and  thyroidismus  are  placed  in  parallel 
columns,  so  that  the  antagonistic  symptoms  as  well  as 
those  which  are  common  to  both  can  be  easily  compared : 


204 


THE    THYKOID    AND    PARATHYROID    GLANDS. 


Myxedema. 


Absence   or   atrophy   of   the 
thyroid  gland. 

Slow,  small,  regular  pulse. 

Torpid,    stolid,     stupid    ex- 
pression. 

Xarrowed  fissure  of  the  eye- 
lids.  "* 


Slowness    of    digestion    and 
excretion,  poor  appetite. 

Reduced  metabolism. 

Thick,   opaque,    flabby,   dry, 

scaly  skin. 
Fingers     short     and     thick, 

often  spadelike. 
Drowsiness  and  somnolence. 

Slowness  of  perception  and 

decreased  sensation  and 
action. 

Slowness  of  thought. 


Want  of  activity  and  slow- 
ness of  motion. 
Stiffness  of  the  extremities. 


Arrested  development  of  the 
bones,  short,  thick,  often 
deformed   bones. 

Continuous  feeling  of  cold. 

Slow  difficult  breathing. 


Increase  of  body  weight. 
Premature  aging. 


Electrical   resistance   of  the 

skin  diminished. 
Temperature   subnormal. 

The  bowels  constipated. 


Basedow's  Disease. 

Diffuse  swelling  of  the 
gland,  hypervasculation, 
hyperplasia. 

Rapid,  dilated,  sometimes 
irregular  pulse. 

Anxious,  unsteady  expres- 
sion; when  the  gaze  is 
fixed  fierce  expression. 

Widened  fissures  of  the 
eyelids,  exophthalmos. 


Abundant  excretion,  gen- 
erally abnormally  large 
appetite. 

Increased  metabolism. 

Thin,  transparent,  injected 
damp  skin. 

Long,  slender  fingers  with 
pointed  ends. 

Insomnia  and  disturbed 
sleep. 

Increased  sensation,  percep- 
tion and  action. 

Rapidity  of  thought,  psy- 
chical disturbances,  hal- 
lucinations, mania,  mel- 
ancholia. 

Continuous  activity  and 
rapidity  of  motion. 

Trembling  of  the  extremi- 
ties, increased  motility  of 
the  joints. 


Thyroidismus. 


Rapid,     dilated, 
weak  pulse. 


Widened  fis- 
sures of  the 
eyelids,  ex- 
opthalmos. 

Abundant  ex- 
cretion. 

Increased      me- 
tabolism. 
Damp  skin. 


Xervousness,  rr- 
ritabilitv. 


Paralysis  of 

one  or  more 
limbs,  mus- 
cular weak- 
ness. 


Slender  skeleton,  here  and 
there  soft  and  thin  bones. 

Unbearable  feeling  of  heat. 

Superficial  breathing  with 
defective  inspiratory  ex- 
pansion of  the  chest. 

Decrease  of  body  weight. 

Youthful  appearance  in  the 
commencement  of  the  dis- 
ease. 

Electrical  resistance  of  the 
skin  increased. 

Temperature    normal     with  I  Temperature  in- 


Flushings,  feel- 
ing of  heat. 


Decrease     of 
body  weight. 


occasional  increase. 
Diarrhea  the  rule. 


creased. 
Diarrhea  the 
rule. 


BASEDOW   S    DISEASE. 


205 


Myxedema. 


Thyroid  feeding  cures. 

Skin  dry,  cold,  sweating  ab- 
sent. 


Characteristic  edema  of  the 

skin. 
Loss  of  the  hair  of  the  head 

and  eyebrows  usually  not 

complete. 
Dryness  of  the  hair,   single 

hairs  thick  and  rough. 

Loss  of  hair  rarely  complete. 

Pigmentation  of  the  skin 
yellow  to  brown,  seldom 
dark,  affects  the  whole 
body. 

Pigmentation  usually  most 
marked  on  eyelids,  fore- 
head, face,  lips,  nose  and 
breasts. 

Reduced  secretion  of  saliva. 

Reduced  tear  secretion  rare- 
ly increased. 

Want  of  feeling  in  the  ex- 
tremities common. 

Tiredness  in  the  legs. 


Basedow's  Disease. 


Thyroid  feeding  usually  in- 
creases symptoms. 

Sweatings,  flushings,  tre- 
mors, palpitation,  in- 
creased pulse. 

A  characteristic  edema. 

Loss  of  the  hair  of  the  head 
and  eyebrows  often  com- 
plete. 

Hair  dry,  single  hairs  thin 
and  rough. 

Loss  of  hair  often  very  ex- 
tensive. 

Pigmentation    of    the    skin 
generally  brown,  often  in 
patches,    resembling    Ad- 
dison's disease. 

Pigmentation  usually  most 
marked  on  eyelids,  fore- 
head, lips,  breasts,  axillae, 
region  of  umbilicus,  neck. 

Reduced  secretion  of  saliva 
seldom. 

Reduced  tear  secretion  often 
increased. 

Want  of  feeling  in  the  ex- 
tremities seldom. 

Tiredness  mostly  very  mark- 
ed in  the  lees. 


Thyroidismus. 


Sweatings, 
flushings,  tre- 
mors, palpi- 
tation, in- 
creased pulse. 


Hair  becomes 
dry  and  falls 
out. 


The  symptoms  which  are  directly  opposite,  are  more 
numerous  and  more  important,  while  those  in  which  the 
two  diseases  resemble  one  another  are  principally  in  con- 
nection with  the  skin.  The  edema  of  Basedow's  disease 
is,  however,  hardly  the  same  as  the  pseudoedema  of  myx- 
edema. The  former  is  often  an  irregular  condition  ap- 
pearing in  various  parts  of  the  body,  rapidly  disappear- 
ing, and  which  is  described  for  want  of  a  better  term  as 
"nervous  edema."  In  both  diseases  there  are  the  lipo- 
matous  swellings  in  the  supraclavicular  region  and  else- 
where, but  they  are  by  no  means  so  common  in  Basedow 's 
disease  as  in  myxedema.     The  swelling  of  the  lips  and 


206  THE    THYEOID   AND    PAEATHYEOID    GLANDS. 

tongue  is  apparently  the  same,  but  in  myxedema  it  is 
probably  due  to  the  pseudoedema,  while  in  Basedow 's  dis- 
ease it  is  the  result  of  a  congestion.  As  Basedow 's  disease 
often  passes  into  a  myxedema  as  the  result  of  the  atrophy 
of  the  thyroid  gland  those  symptoms  which  are  the  same 
in  both  diseases  may  be  really  the  first  symptoms  of  the 
myxedematous  cachexia.  The  fact  that  many  cases  of 
Basedow's  disease  are  improved  by  the  administration  of 
thyroidin  or  phosphoric  acid  goes  to  show  that  in  some 
cases  there  is  a  pathologic  condition  of  the  thyroid  secre- 
tion and  suggests  the  possibility  that,  in  spite  of  the  ap- 
parent hypersecretion  of  the  gland,  there  may  be  an 
absence  of  normal  secretion  producing  myxedema,  or  pos- 
sibly that  the  gland  possesses  a  double  function,  one  of 
which  may  be  perverted  or  lost  while  the  other  is  increased 
or  normal.  Eecently  Ecker,  Faure,  v.  Jaksch,  Mackenzie 
and  others  have  observed  symptoms  of  tetany  in  long 
standing  cases  of  Basedow's  disease  or  after  operation. 
It  is  possible  that  these  symptoms  may  be  the  result  of 
lesions  of  the  parathyroids.  Others  again  claim  that 
Basedow's  disease  is  primarily  a  disease  of  the  parathy- 
roids and,  it  is  claimed,  that  good  results  have  been  ob- 
tained by  parathyroid  feeding.  It  seems  not  improbable 
that  some  of  the  symptoms  at  least  may  be  due  to  a  path- 
ologic condition  of  these  glands. 

The  theory  that  the  hypersecretion  of  the  thyroid  gland 
is  the  principal  factor  in  the  production  of  the  symptoms 
of  Basedow's  disease  has  been  confirmed  by  the  recent 
experiments  of  Edmunds,  detailed  in  a  previous  chapter. 
He  was  able  to  produce  many  of  the  symptoms  in  mon- 
keys by  thyroid  feeding,  and  Xotkin  reports  the  case  of  a 
patient  which  was  diagnosed  as  a  case  of  Basedow's  dis- 
ease, it  being  subsequently  discovered  that  he  had  been 
taking  enormous  quantities  of  thyroid  for  obesity.  M. 
Gagnevin,  a  healthy  medical  student,  took  full  doses  of 


Basedow's  disease.  207 

thyroid  for  eight  days  under  the  supervision  of  Dr.  Combe, 
of  Lausanne,  and  suffered  from  palpitation,  increased  fre- 
quency of  heart 's  action,  tremors,  sweatings,  flushings  and 
exophthalmos. 

ETIOLOGY. 

The  arguments  against  the  theory  of  the  hypersecretion 
of  the  thyroid  gland  being  the  cause  of  Basedow 's  disease 
are  clinical  rather  than  scientific.  It  is  argued  that  the 
former  theory  is  based  upon  two  postulates.  First,  that 
the  symptoms  produced  by  large  doses  of  thyroid  are  sim- 
ilar to  the  symptoms  of  Basedow's  disease.  Second,  that 
the  symptoms  of  myxedema  the  result  of  hypothyroidea 
are  largely  the  antitheses  of  Basedow's  disease. 

As  to  the  first  point  it  is  argued  that  an  atypical  Graves 
disease  is  not  produced  by  thyroid  feeding  but  only  a  few 
symptoms  which  simulate  but  are  not  identical  with  those 
of  Basedow's  disease  and  that  the  same  symptoms  can  be 
produced  by  the  continued  administration  of  other  animal 
extracts,  especially  the  parotid,  that  the  symptoms  pro- 
duced by  thyroid  feeding  resemble  those  of  overdoses  of 
the  nitrites  and  allied  drugs. 

On  the  second  point  it  is  argued  that  though  the  symp- 
toms of  hypothyroidin  as  seen  in  myxedema  are  the  op- 
posite of  those  of  Basedow's  disease  it  by  no  means  neces- 
sarily follows  that  the  latter  disease  is  the  result  of  hyper- 
thyroidea  and  further  that  there  is  no  other  known  ex- 
ample of  a  specific  disease  due  to  hypersecretion  on  the 
part  of  any  gland  whatever.  Hypersecretion  of  any  gland 
as  far  as  is  known  is  the  result  of  some  agent  in  the  blood 
and  not  of  the  gland 's  self-excitation.  In  parenchymatous 
goitre  a  blood  poison  is  undoubtedly  present  which  the 
gland  had  no  share  in  producing,  however  much  the  gland 
may  be  affected. 

The  objections  to  the  theory  of  hypersecretion  of  the 
thyroid  being  the  cause  of  Basedow's  disease  are  worthy 


208  THE    THYROID   AND    PAEATHYEOID    GLANDS. 

of  great  consideration.  The  severity  of  the  symptoms  of 
Basedow's  disease  bears  no  relation  to  the  degree  of  thy- 
roid hypertrophy  which  may  reasonably  be  taken  as  a  fair 
index  of  hyperactivity.  The  thyroid  enlargement  differs 
materially  from  parenchymatous  goitre  in  being  variable 
in  size  and  even  disappearing  with  no  corresponding 
change  in  the  general  symptoms,  the  size  of  the  thyroid  is 
further  no  indication  as  to  the  severity  of  the  disease,  and 
that  all  the  symptoms  of  severe  Basedow's  disease  may 
occur  in  cases  where  the  thyroid  is  not  palpably  enlarged 
as  in  the  so-called  masked  cases  described  later. 

From  the  above  it  is  argued  that  the  enlargement  of  the 
thyroid  is  a  secondary  and  not  a  primary  element  in  the 
etiology  of  the  disease,  the  result  of  overstimulation  of 
the  normal  function  of  the  gland  or  neutralizing  certain 
blood  poisons  generated  during  digestion  in  excess. 

The  results  of  feeding  in  thyroidectomized  animals  de- 
scribed in  a  former  chapter  has  led  to  the  conclusion  that 
the  function  of  the  gland  is  intimately  connected  with  the 
digestive  processes  and  therefore  that  a  marked  change  in 
the  gland  or  its  secretion  may  be  caused  by  digestive  dis- 
turbances. Thompson  in  his  work  on  Graves'  disease 
strongly  advocates  the  digestive  etiology  of  Basedow's 
disease  and  cites  cases  of  cure  or  improvement  in  which 
the  treatment  has  been  entirely  dietetic  with  relapses  when 
the  regimen  was  neglected. 

In  weighing  up  the  etiologic  theories  of  Basedow's  dis- 
ease it  must  be  remembered  that  spontaneous  enlargement 
or  hypersecretion  of  the  gland  is  more  than  improbable, 
that  toxemia  in  some  form  or  another  is  the  cause  of  nearly 
all  disease,  that  the  functions  of  the  thyroid  are  intimately 
connected  with  metabolism  and  assimilation  and  that  the 
chemical  evidence  of  hyperthyroidea  being  the  cause  of  the 
disease  is  by  no  means  complete.  From  the  evidence  at 
our  disposal  the  etiology  of  Basedow's  disease  may  be' 


Basedow's  disease.  209 

summed  up  to  be  due  to  an  excessive  or  perverted  secre- 
tion of  the  thyroid  gland,  the  result  of  a  toxemia  probably 
produced  in  the  digestive  processes. 

The  prognosis  in  Basedow 's  disease  is  a  matter  of  great 
uncertainty.  Usually  the  disease  runs  a  chronic  course, 
with  intermissions  of  temporary  improvement.  In  a  few 
cases  the  disease  subsides  spontaneously,  but  as  a  rule  the 
cure  is  far  from  complete,  the  symptoms  subsiding  to  a 
certain  point  and  remaining  stationary  followed  by  severe 
relapse.  Rarely  the  disease  begins  suddenly  and  subsides 
rapidly.  In  other  cases  the  disease  progresses  more  or 
less  slowly,  but  steadily,  terminating  in  death.  In  those 
cases  where  the  patient  dies  from  the  disease  itself  and  not 
from  some  intercurrent  complication  death  is  gradual  but 
occasionally  sudden. 

There  are  five  cardinal  symptoms  of  Basedow 's  disease, 
increased  action  of  the  heart,  enlargement  of  the  thyroid 
gland,  prominence  of  the  eyeballs,  tremors,  nervous  irri- 
tability or  a  condition  of  general  nervousness,  besides 
which  the  following  symptoms  may  be  present: 

Cardinal  Symptoms.— Increased  action  of  the  heart,  pal- 
pitation, throbbing  of  the  vessels,  etc., 

Enlargement  of  the  thyroid, 

Prominence  of  the  eyeballs, 

General  nervousness, 

Fine  rhythmical  vibratory  tremor. 
Digestive  Organs. — Diarrhea, 

Vomiting, 

Loss  of  appetite,"  bulimia,  sudden  fits  of  hunger, 

Thirst, 

Jaundice. 
Respiratory  Organs.— Cough, 

Increased  frequency  of  respiration, 

Diminished  inspiratory  expansion. 
14 


210  THE    THYROID    AND    PAKATHYEOID    GLANDS. 

Nervous  System.— Yon  Graefe's  symptom, 

Stellwag  's  symptom, 

Defective  convergence  (Mobius), 

Ophthalmoplegia  externa, 

Paralysis,  a  peculiar  form  of  paraplegia, 

Epileptiform  convulsions,  chorea, 

Headache,  neuralgia,  angina  pectoris, 

Psychical  derangements,  depression,  mania,  etc. 
Integumentary  System.— Sweatings,  flushings,  sensations 
of  heat,  rises  in  temperature, 

Diminished  electrical  resistance, 

Increased  pigmentation, 

Leucoderma, 

Loss  of  hair,  atrophy  of  nails. 
Urina ry  System. — Polyuria, 

Albuminuria, 

G-lycosuria, 

Hyperazoturia, 

Phosphaturia,  (?) 

High  uric  acid. 
Generative  System.— Menstrual  derangements, 

Loss  of  sexual  desire,  impotence. 
General.— Debility,    loss    of    weight,    anemia,    cachexia, 
edema  of  lower  extremities. 

Murray  and  Kocher  are  very  decided  in  their  statements 
that  without  enlargement  of  the  thyroid  gland  Basedow's 
disease  cannot  exist,  and  in  my  experience  this  is  true  in 
the  very  great  majority  of  cases.  I  am,  however,  con- 
vinced that  cases  do  occur  where  there  is  probably  a  very 
marked  hypersecretion  of  the  gland  without  any  palpable 
enlargement;  that  the  enlargement  of  the  gland  may  be 
posterior  or  that  the  hypersecretion  may  be  due  to  acces- 
sory glands  is  possible;  the  palpation  of  the  gland  is  ad- 
mittedly attended  with  difficulty,  and  any  slight  enlarge- 


Basedow's  disease.  211 

ment  may  easily  escape  detection.  Byrom  Bramwell 
claims  that  in  10  of  his  79  cases  thyroid  enlargement  was 
absent. 

In  a  typical  case  the  size  of  the  gland  may  vary  from 
being  hardly  palpable  by  the  practiced  diagnostician  to 
the  size  of  a  goose  egg,  in  which  cases  the  isthmus  and  the 
pyramid  and  the  accessory  glands  are  also  enlarged. 

The  enlarged  gland  is  of  variable  consistence,  depend- 
ing upon  its  vascularity.  It  is  usually  firm  and  elastic  if 
the  swelling  is  of  some  duration.  If  examined  soon  after 
its  appearance  it  may  be  soft  and  not  uniform,  some  parts 
not  being  vascular,  but  firmer  and  harder  than  others.  It 
is  rare  that  the  hyperplastic  struma,  the  common  form, 
presses  on  the  trachea  sufficiently  to  produce  dyspnea; 
the  dyspnea  when  marked  is  of  cardiac  origin.  The  vas- 
cular struma,  or,  as  Kocher  prefers  to  call  it,  the  telean- 
gretoid  struma,  is  characteristic  in  its  symptoms. 

The  circulatory  changes  in  the  enlarged  gland  are  usu- 
ally very  apparent,  the  gland  pulsates  in  a  manner  sug- 
gesting aneurysm,  sometimes  combined  with  a  lifting 
movement  of  the  whole  gland,  due  to  the  pulsations  of  the 
carotids.  The  gland  can  be  compared  to  an  elastic  cap- 
sule filled  with  enlarged  vessels,  through  which  the  blood 
stream  is  passing  with  abnormal  rapidity  on  account  of 
the  increased  heart's  action,  producing  a  marked  diastole 
followed  by  a  systole.  So  great  is  the  dilatation  of  the 
vessels  in  severe  cases  that  the  arteries  can  be  seen  to 
pulsate  and  the  branches  of  the  superior  thyroid  artery  can 
be  traced  through  their  tortuous  course  on  the  surface 
of  the  gland  by  palpation.  The  veins  of  the  gland  some- 
times pulsate,  as  do  also  the  large  vessels  of  the  neck.  In 
severe  cases  the  pulsation  of  the  gland  veins  is  a  negative 
pulse,  due  to  the  dilatation  of  the  vessels,  the  increased 
circulation  and  the  weakness  of  the  vessel  walls. 

On  auscultation  there  is  a  distinct  blowing  murmur 


212  THE    THYROID    AXD    PARATHYROID    GLANDS. 

present  over  the  gland  and  vessels,  the  intensity  of  which 
varies  with  the  severity  of  the  disease ;  it  is  short  or  long 
and  sometimes  continuous,  systolic  in  point  of  time,  and 
when  continuous  is  emphasized  in  systoles.  It  is  best 
heard  over  the  trunk  of  the  arteries,  especially  in  the 
superior  thyroid  arteries;  should  the  arteria  ima  or  pyra- 
midalis  be  present  the  murmur  can  be  heard  over  them. 
The  murmurs  are  not  usually  heard  over  the  whole  gland, 
but  only  in  places ;  where  vascularity  is  most  marked  com- 
pression of  the  gland  usually  increases  the  murmur. 

Combined  with  the  murmur  is  another  symptom  which 
is  often  present,  viz :  a  friction  thrill  which  can  be  felt  on 
palpation  occasionally  over  the  whole  gland,  but  usually 
only  in  the  vascular  portions  and  over  the  artery  where 
the  murmur  is  loudest.  Both  the  murmur  and  the  fric- 
tion sound  are  due  to  the  rapid  circulation  and  to  the  swirl 
of  the  blood  stream  as  it  passes  from  a  narrow  into  a 
wider  vessel. 

The  vessels  are  very  much  enlarged,  especially  those 
arteries  which  supply  the  vascular  portion  of  the  struma ; 
if  the  whole  gland  is  affected  then  all  four  arteries  are 
dilated,  as  are  also  the  arteria  ima  and  pyramidalis  when 
present.  Should  the  hyperemia  be  reduced  the  arteries 
will  return  to  the  normal  size,  providing  the  case  is  not 
one  of  too  long  standing.  Hand  in  hand  with  the  increase 
of  the  arteries  goes  an  increase  in  the  size  of  the  veins, 
but  often  not  to  the  same  extent,  the  veins  being  full  and 
only  in  severe  cases  dilated.  Occasionally  when  the 
struma  is  compressed,  owing  to  its  being  extended  into 
the  upper  opening  of  the  thorax,  the  veins  of  the  throat 
and  the  superficial  veins  of  the  breast  become  dilated.  In 
long  standing  cases  the  jugulars  may  become  dilated. 
The  walls  of  the  veins  and  arteries  become  thin  and  weak, 
which  cannot  be  diagnosed  clinically,  but  is  a  point  to  be 
remembered  during  a  surgical  operation.      The  micro- 


Basedow's  disease.  213 

scopical  examination  of  the  walls  of  the  vessels  show  a 
reduction  of  the  elastic  fibres  and  a  space  between  the 
intima  and  adventitia. 

Another  symptom  is  that  the  struma  can  be  partially 
emptied  of  blood  by  pressure,  returning  to  its  original  size 
as  soon  as  the  pressure  is  removed.  It  is  improbable,  ac- 
cording to  Kocher,  that  pressure  on  the  gland  causes  an 
increased  outflow  of  colloid  into  the  system,  which  many 
operators  consider  the  cause  of  occasional  sudden  fatal 
results  from  operative  procedures.  In  many  cases  the 
patients  have  themselves  on  several  occasions  reduced  the 
goitre  by  pressure  without  any  untoward  results. 

The  etiology  of  the  hypervascularity  of  the  gland  and 
the  enervation  of  the  vessels  must  be  connected  with  the 
primary  cause  of  the  disease.  A  vessel  nerve  degenera- 
tion has  been  recorded  by  Guttman  and  Gerhardt  but 
why  the  nerves  of  the  thyroid  vessels  should  be  especially 
attacked  is  a  question  which  cannot  yet  be  answered. 

The  heart  fluctuates  in  size  in  the  majority  of  cases  and 
is  dilated  in  about  30  per  cent,  depending  on  the  severity 
of  the  disease.  Tachycardia  is  one  of  the  cardinal  and 
most  pronounced  symptoms  of  the  disease  which  is  always 
present,  and  may  vary  from  90  to  250  pulsations  per  min- 
ute and  in  some  cases  is  arhythmic ;  attacks  of  angina  pec- 
toris are  not  uncommon;  the  apex  beat  is  diffuse  and 
increased  in  force ;  in  severe  cases  the  whole  of  the  car- 
diac area  pulsates  visibly,  the  pulsation  passing  along  the 
main  arteries  producing  a  marked  epigastric  pulsation. 
In  very  severe  cases  the  whole  thorax  may  pulsate  while 
the  patient  is  at  rest,  being  so  severe  as  to  produce  move- 
ment of  the  head.  Palpitation  may  also  be  very  severe 
but  is  by  no  means  a  constant  cause  of  complaint;  it  is 
usually  the  first  symptom  of  which  the  patient  complains 
and  is  constant,  fluctuating  in  degree,  being  usually  more 
severe  in  the  morning. 


214  THE    THYROID    AND    PARATHYROID    GLANDS. 

The  heart  sounds  are  accentuated  but  an  abnormality 
can  seldom  be  detected.  Murmurs  and  friction  sounds  are 
common,  varying  with  the  irritation  and  rapidity  of  the 
heart,  but  valvular  insufficiencies  can  rarely  be  detected. 

As  stated  above,  the  pulse  is  rapid,  and  throbbing  of 
the  vessels  in  the  head  and  neck  are  often  complained  of, 
causing  great  discomfort.  The  pulse  is  usually  small  in 
size  and  regular;  at  times  it  is  dicrotic  and  in  the  latest 
stages  of  the  disease  it  may  become  irregular  or  intermit- 
tent. Besides  the  murmurs  heard  over  the  vessels  of  the 
neck,  murmurs  can  occasionally  be  heard  over  the  smaller 
arteries,  as  the  brachial  and  crural ;  there  is  a  distinct 
capillary  pulse.  Hemorrhage,  epistaxis,  bleeding  of  the 
gums,  pulmonary  hemorrhage  may  occur.  Varicose  veins 
and  hemorrhoids  are  common.  Becker 's  retinal  pulse  and 
Gerhardt's  liver  and  spleen  pulsation  have  been  occasion- 
ally observed.  In  long  standing  cases  edema  of  the  feet 
and  ankles  may  occur. 

Prominence  of  the  eyeballs,  exophthalmos,  which  is 
usually  bilateral,  rarely  unilateral,  is  one  of  the  most 
prominent  symptoms,  being  rarely  absent  in  well  marked 
cases.  When  the  exophthalmos  is  marked  and  the  upper 
lid  spasmodically  contracted,  as  sometimes  happens,  there 
is  a  typical  staring  look  which  gives  a  fierce  or  frightened 
expression  to  the  face.  So  great  may  be  the  protrusion  of 
the  eyeballs  that  the  recti  muscles  become  visible,  and 
cases  are  on  record  where  the  eyeball  has  become  dislo- 
cated from  the  orbit  and  had  to  be  replaced  with  the 
finger.  The  exophthalmos  varies  according  to  the  emo- 
tional condition  of  the  patient,  any  excitement  causing  it 
to  increase.  A  school  teacher  stated  that  she  first  became 
aware  of  the  exophthalmos  by  her  pupils  becoming  fright- 
ened by  her  appearance ;  this  no  doubt  was  partially  due 
to  the  normal  retraction  of  the  lid  which  takes  place  dur- 
ing excitement.     The  protrusion  may  be  so  great  that  the 


Basedow's  disease.  215 

eyelids  are  unable  to  close  over  the  eyeball,  producing 
conjunctivitis  and  ulceration  of  the  cornea,  but  as  a  rule 
the  eyesight  is  but  little  affected,  the  retinal  vessels  are 
dilated  and  occasionally  pulsate.  Spasm  of  the  fibres  of 
Muller's  muscle  and  the  accumulation  of  fat  behind  the 
eye  in  the  orbit,  with  dilatation  and  engorgement  of  the 
vessels  back  of  the  eye  are  often  given  as  causes^  The 
pupils  are  usually  normal,  but  may  sometimes  be  dilated, 
they  may  be  unequal ;  the  absence  of  any  marked  change 
in  the  pupils  seems  to  oppose  the  theory  that  the  exoph- 
thalmos is  due  to  a  lesion  of  the  sympathetic.  Stellwag  's 
sign  is  the  contraction  of  the  upper  lid,  which  is  probably 
due  to  spasm  of  Muller's  muscle.  The  spasmodic  con- 
traction of  the  lid  varies  in  degree  and  causes  the  aperture 
between  the  lids  to  be  wider  than  normal.  This  is  not  a 
constant  symptom,  but  is  of  importance,  though  it  has 
been  observed  occasionally  in  cases  where  Basedow's  dis- 
ease did  not  exist.  Absence  of  blinking  occurs  in  about 
5  per  cent  of  the  cases.  Von  Graefe's  sign  consists  in  the 
upper  lid  failing  to  follow  the  eyeball  in  a  steady  coordin- 
ate manner,  the  lid  only  following  the  downward  move- 
ment of  the  eyeball  in  irregular  jerks.  This  symptom  can 
be  observed  by  fixing  the  patient's  gaze  on  an  object  above 
the  level  of  the  eye  and  slowly  lowering  the  object  towards 
the  ground,  when  the  failure  of  the  lid  to  follow  the  eye- 
ball can  easily  be  seen.  This  symptom  is  present  in  about 
50  per  cent  of  the  cases.  Mobius'  symptom  consists  in 
the  patient  being  unable  to  converge  for  near  objects  and 
is  present  in  about  25  per  cent  of  cases. 

One  of  the  most  constant  and  important  symptoms  is 
the  muscular  tremor  first  described  by  Marie  and  Charcot, 
consisting  of  fine  rhythmical  tremors  about  eight  or  nine 
to  the  second  or  twice  as  rapid  as  the  tremors  of  paralysis 
agitans.  The  muscles  usually  affected  are  those  of  the 
upper  and  lower  limbs,  though  occasionally  the  whole  body 


216  THE    THYROID    AND    PAEATHYEOID    GLAXDS. 

trembles  and  can  be  felt  by  placing  the  band  upon  the 
shoulder.  Charcot  mentions  that  the  individual  digits  do 
not  tremble,  which  he  claims  distinguishes  it  from  the 
tremor  of  alcoholism  and  the  general  paralysis  of  the 
insane,  in  which  conditions  the  tremor  is  equally  rapid. 
Occasionally  the  tremor  is  unilateral.  It  can  be  observed 
best  by  extending  the  arm  at  right  angles  to  the  body  and 
placing  a  pencil  between  the  fingers.  In  a  certain  pro- 
portion of  cases  there  is  an  irregular  spasmodic  jerking 
of  the  fingers  and  toes.  The  tremor  usually  does  not 
appear  till  the  palpitation  has  become  marked;  it  is  a 
symptom  of  great  value  in  diagnosing  cases  of  masked 
Basedow's  disease,  which  will  be  described  later. 

The  nervousness  of  the  patient  is  a  very  marked  symp- 
tom, contrasting  with  the  apathy  and  torpor  of  myxedema. 
There  are  a  number  of  what  may  be  termed  "simple" 
psychic  symptoms,  more  or  less  marked,  connected  with 
Basedow's  disease  which  can  be  broadly  classed  under  the 
headings  of  psychic  instability  and  irritability  with  the 
want  of  continuity  of  ideas  resembling  hysteria  or  neuras- 
thenia ;  occasionally  true  hysteria  or  neurasthenia  are  as- 
sociated with  Basedow's  disease  but  the  majority  of  cases 
do  not  present  the  stigmata  associated  with  true  hysteria 
and  neurasthenia  and  are  a  part  of  the  symptom  complex 
of  Basedow's  disease. 

Sooner  or  later  after  the  onset  of  the  disease  the  char- 
acter of  the  patient  changes,  he  becomes  irritable,  selfish. 
peevish,  exacting,  intolerant  of  contradiction,  never  satis- 
fied and  never  recognizing  the  sacrifices  made  for  him  by 
others ;  at  times  he  may  have  periods  of  most  enthusiastic 
gaiety,  changing  almost  suddenly  to  bitterness  and  mel- 
ancholic depression.  Generally  they  have  an  abnormal 
activity,  a  desire  to  continually  change  their  position,  an 
irritability  of  desire,  a  feeling  of  desire,  but  not  knowing 
what  it  is  they  want,  they  are  tormented  by  an  indefinable. 


Basedow's  disease.  217 

incessant  desire  for  change ;  at  one  moment  taciturn  and 
reserved,  they  almost  suddenly  become  loquacious,*  speak- 
ing with  a  singular  and  apparently  forced  volubility,  sup- 
porting theories  contrary  to  their  normal  views  with 
spasmodic  energy,  often  almost  fiercely,  forgetting  the 
courtesies  of  argument  and  at  the  slightest  contradiction 
becoming  rude  and  irate.  In  time  these  psychic  symp- 
toms which  have  been  happily  described  as  "psychic 
chorea"  become  accentuated,  the  patient  may  suddenly 
develop  a  most  marked  aversion  for  some  member  or 
members  of  the  family  without  any  apparent  reason 
which  no  amount  of  explanation  or  argument  can  over- 
come. More  rarely  the  patient  is  habitually  depressed, 
continually  occupied  with  the  contemplation  of  his  own 
troubles  he  becomes  taciturn  and  morose ;  as  a  rule  Trous- 
seau's  description,  "la  maladie  de  Basedow  est  une  colere 
perpetuelle, "  is  correct. 

Insomnia  and  nightmares  are  almost  invariably  present, 
adding  to  the  mental  and  nervous  instability ;  the  memory 
becomes  defective  in  chronic  cases,  details  escape  and  be- 
come mixed,  scientific  data  and  words  of  a  foreign  lan- 
guage are  the  first  to  be  forgotten;  in  severe  cases  the 
memory  may  become  so  defective  that  the  patient  forgets 
what  he  has  read  only  three  or  four  lines  above,  making 
reading  valueless. 

Will  power  is  as  a  rule  not  affected ;  it  may  be  dimin- 
ished and  very  rarely  abolished.  In  most  cases,  however, 
the  patient  is  changeable,  forming  different  and  often  con- 
tradictory resolutions  at  short  intervals. 

These  psychic  symptoms  become  more  and  more  ac- 
centuated, the  patient  at  times  passing  the  border  line  and 
becoming  insane.  Many  observers  have  considered  the 
occurrence  of  insanity  in  Basedow's  disease  as  a  coinci- 
dence, each  disease  developing  separately  and  from  sep- 
arate pathologic  conditions,   arguing  from  the  insanity 


18  THE    THYKOID    AND    PAEATHYEOID    GLANDS. 

being  of  various  kinds — hysteria,  epilepsy,  alcoholism, 
mania  and  melancholia— which  progress  finally  to  de- 
mentia. 

The  theory  of  the  duality  of  the  disease  is  not  borne  out 
by  clinical  examination;  insanity  may  develop  for  the 
reason  that  the  nervous  and  mental  condition  is  enfeebled, 
but  it  is  by  no  means  uncommon  for  the  insanity  and  Base- 
dow 's  disease  to  develop  at  the  same  time,  the  insanity 
subsiding  with  the  other  symptoms.  In  some  cases  of 
insanity  the  Basedowic  symptoms  develop  only  after  some 
time,  in  which  case  they  may  have  been  latent,  masked  or 
incomplete  and  have  been  the  primary  cause  of  the  in- 
sanity, or  they  have  developed  independently  of  the  in- 
sanity.. 

The  form  of  insanity  supervening  in  Basedow's  disease 
is  most  frequently  depressive  mania,  exaltation  rarely 
occurring,  melancholia  and  delusions  of  persecution  re- 
sembling paranoia.  In  a  case  diagnosed  as  paranoia 
which  came  to  autopsy  the  thyroid  was  found  much  en- 
larged, weighing  94  grams,  though  no  enlargement  had 
been  observed  during  life. 

The  insanity  of  Basedow's  disease  is  attributed  by 
Hirschl  to  changes  in  the  cerebral  circulation  (probably 
the  cause  of  all  the  insanities).  Jacquim  considers  it  due 
to  the  emaciation  and  weakness  when  the  nutrition  is  poor 
and  the  continued  vomiting  and  insomnia  have  weakened 
the  nervous  system.  In  his  opinion  insanity  plays  the 
same  role  in  Basedow's  disease  as  delirium  in  typhoid 
fever.  Most  observers  ascribe  the  mental  symptoms  to 
the  diseased  condition  and  hypersecretion  of  the  thyroid. 

Direct  experiment  upon  the  human  as  to  the  effect  of 
excessive  thyroid  feeding  on  mentality  is  of  course  impos- 
sible, but  several  cases  are  on  record  where  mental  symp- 
toms have  been  produced  by  accidental  overdosing  with 
thyroid. 


Basedow's  disease.  219 

Dr.  Boinet  in  the  8 emetine  medicate,  1899,  records  the 
case  of  a  man  suffering  from  exfoliating  general  derma- 
titis who  took  large  doses  of  thyroid,  followed  by  palpita- 
tion, trembling  of  hands,  increase  in  size  of  thyroid,  with 
psychic  symptoms  of  delusions  of  persecution  and  mental 
confusion,  which  disappeared  on  the  treatment  being  sus- 
pended. Dr.  Ferrarini  treated  a  woman  for  obesity  with 
large  doses  of  thyroid.  She  developed  mental  confusion, 
motor  disturbances,  depression,  tremor  and  increased 
pulse  rate;  the  symptoms  disappeared  on  the  suspension 
of  the  drug. 

Headache  is  a  severe  cause  of  complaint,  neuralgia  is 
common,  the  condition  as  to  sleep  is  variable,  migraine, 
angina  pectoris,  epilepsy  and  chorea  occur  as  develop- 
ments during  the  disease.  Charcot  describes  a  special 
form  of  paraplegia  which  is  peculiar  to  the  disease.  The 
parlysis  is  usually  incomplete  but  may  be  absolute,  the 
muscles  are  placid  and  atrophied,  the  reflexes,  deep  and 
superficial,  are  abolished,  there  are  no  twitchings,  sensi- 
bility and  electrical  reactions  are  normal  and  the  bladder 
and  rectum  under  control.  There  is  a  sudden  giving 
away  of  the  legs,  due  to  an  unexpected  flexion  of  the  knees, 
which  is  characteristic  of  the  condition.  The  paraplegia 
is  functional  and  is  not  permanent;  from  the  fact  that 
there  are  no  sensory  disturbances  it  does  not  appear  to 
be  typical. 

In  a  considerable  proportion  of  cases  of  Basedow's  dis- 
ease there  is  developed  a  pigmentation  of  the  skin  distrib- 
uted in  patches  or  general,  the  genital  organs,  the  areolae 
of  the  nipples  and  around  the  orbits  are  usually  darkest 
and  may  be  the  only  places  where  the  discoloration  takes 
place.  There  is  a  peculiar  dirty,  dingy,  yellowish  brown 
appearance  of  the  skin  of  the  face  and  more  or  less  of  the 
whole  body.  The  pigmentation  in  one  form  or  another 
occurs  in  about  40  per  cent  of  the  cases,  and  where  goitre 


220  THE    THYROID    AND    PARATHYROID    GLANDS. 

and  exophthalmos  are  absent  is  of  considerable  diagnostic 
value.  Patches  of  leucoderma,  urticaria,  eczema,  ery- 
thema and  other  skin  eruptions  have  been  observed  in 
about  10  per  cent  of  the  cases. 

There  is  diminished  electrical  resistance  of  the  skin, 
which  is  in  marked  contrast  to  the  increased  resistance  in 
myxedema.  This  diminished  resistance  is  probably  due 
to  the  dilated  capillary  vessels  which  keep  the  epidermis 
bathed  in  fluid,  the  consequent  sweating  keeping  the  skin 
moist.  TVolfenden  found  that  the  average  electrical  re- 
sistance of  the  normal  skin  was  from  4000  to  5000  ohms, 
while  in  Basedow 's  disease  he  found  it  as  low  as  200  and 
in  eight  cases  the  highest  was  only  500  to  700.  In  alcohol- 
ism and  akromegaly  there  is  also  a  marked  decrease  in  the 
electrical  resistance,  but  not  to  anything  like  the  extent  as 
the  above  observations  indicate. 

The  hair  falls  out  and  becomes  thin  in  about  20  per 
cent  of  the  cases  and  atrophic  changes  occur  in  the  nails 
in  a  few  cases ;  both  these  symptoms  are  probably  due  to 
the  anemia  rather  than  to  the  disease  itself. 

The  respiratory  symptoms  are  a  short,  deep,  nervous 
cough,  occurring  in  about  16  per  cent  of  the  cases ;  rarely 
a  profuse  pink  watery  secretion  pours  out  from  the  bron- 
chial mucous  membrane.  Increased  frequency  of  respira- 
tion occurs,  due  to  anemia,  cardiac  complication  or  is 
possibly  of  nervous  origin.  Bayson's  symptom  has  been 
observed,  viz :  a  diminished  expansion  of  the  chest  during 
inspiration.  Air  hunger  is  common,  the  result  of  the 
anemia ;  there  is  also  a  weakening  of  the  voice  in  a  number 
of  cases. 

The  lips  are  sometimes  swollen  and  congested,  bleeding 
easily,  sometimes  with  a  continuous  tremor,  which  is  in- 
creased while  speaking ;  the  tongue  is  swollen,  the  papilla? 
enlarged  and  of  a  bluish  color,  vibrating  tremors  are  often 
present.     There  is  a  great  increase  in  the  secretion  of  the 


Basedow's  disease.  221 

saliva  in  some  cases,  in  others  the  patients  complain  of 
dryness  in  the  mouth  and  throat ;  often  there  is  a  difficulty 
in  swallowing,  rarely  due  to  the  pressure  on  the  esophagus 
by  the  goitre  but  to  the  swollen  condition  and  dryness  of 
the  mucous  membranes  of  the  mouth,  pharynx  and  esoph- 
agus, which  are  of  a  bluish  color;  the  gums  are  swollen, 
bleeding  easily;  the  teeth  are  brittle. 

In  about  50  per  cent  of  the  cases  there  is  vomiting, 
which  cannot  be  ascribed  to  stomach  derangements,  as 
the  secretions  are  usually  normal  or  there  may  be  a  slight 
hyperchlorhydria.  In  some  cases  the  vomiting  is  one  of 
the  first  symptoms  of  which  the  patient  complains;  the 
vomiting  may  only  take  place  in  the  morning  when  the 
stomach  is  empty,  quantities  of  mucus  being  ejected 
which  may  be  neutral  or  very  slightly  acid ;  the  vomiting 
is  sometimes  so  severe  as  to  produce  starvation,  when  the 
breath  may  have  the  sweet  odor  of  acetone,  diacetic  acid 
appearing  in  the  urine.  It  has  been  suggested  that  the 
vomiting  of  pregnancy  is  the  result  of  the  increased  secre- 
tion of  the  thyroid. 

Diarrhea  occurs  in  about  50  per  cent  of  the  cases  in 
sudden  paroxysms  without  any  apparent  cause,  persisting 
for  several  days  and  then  disappearing;  the  evacuations 
are  frequent,  copious  and  watery,  containing  much  mucus 
unattended  by  pain  or  colic,  though  in  exceptional  cases 
there  may  be  colicky  pains  before  an  evacuation.  There 
is  said  to  be  a  very  large  elimination  of  phosphates  in  the 
feces.  During  an  attack  the  tongue  is  clean  and  the  appe- 
tite good  or  even  voracious.  Astringents  are  usually  of 
little  value,  the  diarrhea  being  of  circulatory  origin  due  to 
vaso-dilatation.  The  diarrhea,  like  the  vomiting,  may 
only  occur  in  the  morning,  and  in  some  cases  is  followed  by 
obstinate  constipation.     Acholia  is  occasionally  observed. 

Excessive  sweating  is  a  very  characteristic  and  constant 
symptom,  combined  with  flushings  of  the  face,  hands,  feet 


222  THE    THYEOID    AND    PARATHYROID    GLANDS. 

or  body  with  sensations  of  heat,  but  distinct  rise  of  tem- 
perature is  rare.  The  flushings  and  excessive  sweating 
without  increase  of  temperature  are  a  valuable  diagnostic 
symptom,  occurring  in  about  90  per  cent  of  all  cases. 

Enlargement  of  the  lymphatic  glands  and  spleen  has 
been  observed.  In  this  connection  it  is  interesting  to  note 
the  frequency  of  persistence  or  regeneration  of  the  thymus 
in  this  disease.  Eendu,  Johnstone,  Hale  White,  Mobius, 
Marie,  Joff roy,  Schnitzler,  Mackenzie  and  Edmunds,  Gra- 
zone  and  Murray  have  all  pointed  out  the  frequency  of 
this  condition.  Bonnet  reports  20  cases  in  which  this 
abnormality  existed,  coinciding  usually  with  a  hyperplasia 
of  the  lymphatic  tissues. 

Loss  of  weight  is  usually  a  very  prominent  symptom. 
In  severe  cases  not  only  does  the  panniculus  disappear  but 
the  muscles  are  also  affected.  Very  rarely  a  patient  in 
spite  of  vomiting  and  nervous  irritability  will  remain  in 
good  condition,  sometimes  even  gaining  in  weight.  The 
vomiting  is  probably  the  result  of  the  increased  thyroid 
secretion,  as  is  perhaps  also  the  vomiting  of  pregnancy. 
The  loss  of  weight  is  accompanied  by  general  weakness, 
until  the  patient  is  unable  to  do  any  work,  and  finally  is 
confined  to  bed.  A  paraplegia  already  described  results 
with  the  typical  giving  way  of  the  knees.  At  the  com- 
mencement of  the  disease  there  is  usually  a  feeling  of 
tiredness  in  the  muscles  which  renders  all  exertion  a 
burden. 

Menstruation  is  usually  decreased,  though  occasionally 
it  may  be  profuse  but  is  rarely  normal.  The  mammae 
shrink  as  the  disease  progresses  but  there  is  not  a  distinct 
atrophy. 

The  urine  is  usually  normal  or  slightly  increased  in 
quantity,  even  when  polydipsia  is  present,  the  excess  of 
fluid  being  eliminated  by  the  skin.  Glycosuria  occurs  in 
a  few  cases  and  albumin  in  small  amounts  is  often  present, 


Basedow's  disease.  223 

sometimes  with  casts  probably  of  vasomotor  origin.  The 
urea  and  nitrogen  are  much  increased,  the  phosphorus 
elimination  is  sometimes  normal,  usually  much  increased. 
Drechsel  found  that  in  patients  taking  considerable  quan- 
tities of  sodium  phosphate  there  was  no  increase  of  the 
phosphates  in  the  urine,  probably  they  were  eliminated  in 
the  feces ;  the  uric  acid  was  enormously  increased  in  one 
case.  Drechsel  found  5.4  grms.  in  the  24  hours.  This 
may  be  due  to  the  cell  destruction.  The  carbon  nitrogen 
factor  is  low,  oxalic  acid  is  often  slightly  increased,  the 
proportion  of  neutral  sulphur  is  low,  chlorids  are  usually 
low,  bile  pigment  is  often  present,  indol  is  generally  above 
normal.  In  cases  where  there  is  starvation  acetone  and 
diacetic  acid  may  be  present. 

There  is  a  great  aggravation  of  the  cardinal  symptoms 
immediately  preceding  death,  the  mental  symptoms  de- 
velop into  an  acute  delirium  requiring  restraint,  the  tem- 
perature rises  to  103°  and  104°,  the  pulse  and  respiration 
are  greatly  increased.  Vomiting,  diarrhea,  sweating,  der- 
matitis, jaundice  and  convulsions  may  occur.  The  patient 
appears  as  if  the  victim  of  a  nerve  storm,  some  centres 
being  more  affected  than  others.  The  delirium  consists  in 
wriggling  about  the  bed  and  refusing  nourishment ;  severe 
hysterical-like  delusions  and  hallucinations  are  common; 
rarely  is  there  melancholia,  the  patient  ultimately  re- 
lapsing into  a  state  of  complete  lethargy  with  rapid,  catchy 
breathing.  These  final  symptoms  resemble  death  from 
removal  of  parathyroids. 

The  pathology  of  the  thyroid  gland  in  Basedow's  dis- 
ease has  been  the  subject  of  very  careful  study  by  Achard, 
Askanazy,  Brissaud,  Edmunds,  Ehrlich,  Farner,  Green- 
field, Haemig,  Horsley,  Joffroy,  Matheson,  Mobius,  Miiller, 
Renaut  and  others  with  variable  results.  The  most  com- 
mon form  is  parenchymatous  hyperplasia  of  the  gland, 
accompanied  by  structural  changes  and  increased  cell  pro- 


-24  THE    THYROID    AND    PARATHYBOID    GLANDS. 

liferation,  with  changes  of  the  colloid  substance  and  of  the 
stroma.  These  changes  are  characteristic  of  the  tumor 
in  the  majority  of  cases,  but  Farner  and  Haemig  describe 
a  number  of  different  forms  of  struma,  most  of  which 
point  to  a  chemical  change  in  the  secretion.  It  has  been 
suggested  that  the  colloid  substance  becomes  qualitatively 
the  same  as  the  thyroid  mucin,  which  is  the  sole  constitu- 
ent of  the  gland  during  fetal  life.  Ehrlich  and  Farner 
found  the  veins  and  arteries  enlarged,  also  the  capillaries 
were  dilated  and  increased  in  number.  Langhans  consid- 
ers that  there  is  an  increase  in  the  number  of  follicles  in 
nearly  every  case  and  that  the  contents  are  sometimes  in- 
creased, sometimes  diminished,  there  being  apparently  a 
qualitative  change  in  the  composition  of  the  colloid  sub- 
stance. The  changes  in  the  protoplasm  and  nuclei  of  the 
cells  are  not  constant  but  usually  appear  to  be  in  the 
nature  of  a  degeneration.  He  also  found  an  excess  of  col- 
loid in  the  lymph  and  blood  vessels  as  well  as  in  the  stroma 
in  the  majority  of  cases.  In  a  certain  number  of  cases 
there  is  a  mixed  condition  of  parenchymatous  hyperplasia 
and  nodular  formations.  Struma  nodosa  is  rare  and  when 
it  occurs  is  probably  the  result  of  long  standing  disease. 
In  the  mixed  form  the  nodules  are  usually  typical,  rarely 
developing  into  cysts,  the  hyperplasia  is  usually  colloidal, 
seldom  parenchymatous.  Langhans  found  in  the  exam- 
ination of  16  tumors  that  8  were  of  the  diffuse  colloid 
variety,  6  partially  colloidal  and  part  parenchymatous,  2 
wholly  parenchymatous;  the  colloid  substance  being  ap- 
parently normal.  There  is  apparently  no  definite  histo- 
logical lesion  of  the  thyroid  in  Basedow's  disease.  Le- 
sions the  same  as  those  described  above  have  been  found 
in  the  thyroid  glands  of  patients  who  exhibited  no  symp- 
toms of  Basedow's  disease. 

The  question  as  to  the  increase,  decrease  or  qualitative 
change  of  the  colloid  secretion  in  the  disease  is  not  yet 


BASEDOW'S    DISEASE. 


225 


Fig.  75.— Thyroid  gland  in  Basedow's 
disease. 


settled.  Decreased  secretion  or  rather  a  decreased  quan- 
tity of  the  colloid  substance  in  the  gland  has  been  often 
observed.  Oswald,  in  his  analyses  of  glands  from  cases 
of  this  disease,  found  a  decreased  percentage  of  iodin,  but 
agreed  that  as  the  gland  was  increased  in  size  the  total 
be  really  increased.  Far- 
ner's  observation  that  the 
amount  of  thyroidin  might 
stroma,  blood  and  lymph 
vessels  contained  an  ex- 
cessive amount  of  colloid 
points  to  an  increased  elim- 
ination with  or  without  in- 
creased secretion.  Haemig 
and  Ehrlich  are  of  opinion 
that  the  substance  found 
in  the  stroma  and  vessels 
is  either  not  colloid  or  at 

least  not  normal  colloid,  the  latter  considering  that  the 
changes  in  the  colloid  substance  are  due  to  the  increased 
vascularity. 

That  the  tumor  is  due  to  increased  vascularity  there 
can  be  no  doubt;  the  pulsation,  the  murmur  and  above 
all  the  fact  that  ligatures  of  the  arteries  cutting  off  the 
blood  supply  immediately  reduces  the  size  of  the  tumor, 
and  that  pressure  on  the  gland  reduces  the  size,  it  filling 
up  again  on  removal  of  the  pressure,  place  this  point  be- 
yond question. 

In  the  vessels  themselves  there  is  usually  a  thickening 
of  the  intima  and  a  thinning  of  the  media,  the  veins  suf- 
fering in  a  like  manner. 

The  lymphatic  glands  in  the  neck  are  usually  enlarged 
and  also  those  of  the  mediastinum,  pointing  to  a  patho- 
logical condition  of  the  lymphatic  system. 
15 


226  THE    THYROID    AND    PARATHYROID    GLANDS. 

INCOMPLETE    BASEDOW  's    DISEASE. 

As  there  is  an  incomplete  myxedema  so  there  is  an 
incomplete  Basedow's  disease,  which  is  the  result  of  a 
hypersecretion  of  the  thyroid  gland  and  consequent  thy- 
rci-idisnras.  These  cases  vary  from  the  typical  with  all  the 
cardinal  symptoms  to  what  appears  at  first  sight  to  be 
simply  nervousness.  The  tremor  is  nearly  always  present 
to  a  more  or  less  marked  degree,  combined  with  a  pulse 
rate  of  90  or  above ;  the  patient  usually  gives  a  history  of 
having  lost  weight  rapidly,  which  she  ascribes  to  her  ner- 
vous irritability,  the  least  contradiction  or  annoyance 
throws  her  into  a  state  of  excitement ;  fear  is  usually  the 
most  marked  symptom,  which  may  resemble  paranoia  or 
delusional  insanity.  The  appetite  is  poor,  amounting  in 
some  cases  to  absolute  refusal  of  all  food,  often  accom- 
panied with  vomiting  of  mucus.  There  may  be  occasional 
fits  of  hunger  amounting  to  bulimia,  at  other  times  there 
may  be  great  thirst,  the  so-called  nervous  diarrhea,  may 
also  occur.  Associated  with  these  symptoms  are  epilep- 
toid  convulsions,  chorea,  headaches,  neuralgia  and  angina 
pectoris.  In  these  atypical  cases  flushings,  which  the  pa- 
tient calls  rushings  of  blood  to  the  head,  excessive  sweat- 
ing, and  subjective  temperature  are  of  diagnostic  value. 
The  patient  often  complains  of  a  difficulty  in  swallowing. 
A  dirty,  yellowish  pigmentation  of  the  skin  is  often  pres- 
ent, being  a  lighter  shade  than  the  bronzing  of  Addison's 
disease.  I  have  seen  a  case  where  the  tremors,  the  ner- 
vousness and  the  discoloration  of  the  skin  in  patches 
around  the  eyes,  the  nipples  and  on  the  back  of  the  handsr 
with  slight  convulsions,  were  the  main  symptoms.  There 
are  also  usually  irregularities  of  the  menstrual  function. 
In  males  loss  of  sexual  desire  and  impotence  are  common 
causes  of  complaint. 

The  hair  falls  out  in  a  considerable  number  of  cases. 

The  urinary  derangements  are  polyuria,  albuminuria 


INCOMPLETE   BASEDOW'S    DISEASE. 


227 


and  glycosuria,  Diacetic  acid  may  be  present  where  vom- 
iting is  severe,  owing  to  starvation.  The  nitrogen  elim- 
ination is  increased  at  least  in  the  earlier  stages,  being 
markedly  more  than  the  amount  taken  in  the  food. 

Of  the  cardinal  symptoms  of  Basedow's  disease  the 
exophthalmos  is  usually  absent  or  very  slight  and  the 
enlargement  of  the  thyroid  may  not  be  palpable. 


Fig.  76.  Fig.  77. 

Masked   Basedow's   disease  with   slight   exophthalmos. 

The  blood  pressure  is  usually  normal  but  there  is  not 
the  rise  either  in  mean  or  maximum  pressure  which  should 
occur  on  taking  the  erect  position ;  for  example,  in  a  case 
in  which  the  diagnosis  of  atypical  Basedow's  disease  was 
made  the  blood  pressures  were : 

Reclining. — Pulse  95,  mean  p.  101,  maximum  p.  140  = 
0.726. 

Standing.— Pulse  105,  mean  p.  95,  maximum  p.  135  = 
0.703,  showing  that  the  vasomotor  system  was  abnormal. 

The  diagnosis  of  these  cases  has  usually  to  be  made  by 
exclusion,  but  the  abnormal  postural  variations  in  the 


228  THE    THYROID    AND    PARATHYEOID    GLANDS. 

blood  pressure,  the  sweatings,  flushings,  rapid  pulse,  dis- 
coloration of  the  skin,  fine  tremors  and  nervous  irritabil- 
ity are  usually  sufficiently  marked  to  enable  the  physician 
to  make  a  diagnosis. 

Treatment.— The  medicinal  treatment  of  Basedow's  dis- 
ease has  not  so  far  proved  very  satisfactory,  and  the  opin- 
ion of  today  is  in  favor  of  surgical  interference.  Many 
cases  can,  however,  be  improved  and  even  cured  by  careful 
attention  to  details  and  by  the  intelligent  use  of  drugs. 

All  cases  of  peripheral  irritation  should  be  removed  as 
far  as  possible  and  excitement  of  any  kind  avoided,  the 
patient  leading  a  quiet  routine  life,  in  which  nothing 
should  be  attempted  likely  to  increase  the  rapidity  of  the 
heart's  action.  When  the  case  is  severe  the  patient  should 
remain  in  bed.  The  diet  should  be  plain  and  nutritious, 
stimulants,  such  as  tea,  coffee,  alcohol  or  tobacco,  should 
be  forbidden  or  reduced  to  a  minimum.  It  is  not  wise  in 
this  or  any  other  disease  to  absolutely  interdict  habits 
which  are  perhaps  lifelong.  The  worry  of  the  unsatisfied 
desire  for  the  stimulants  is  usually  worse  for  the  patient 
than  their  moderate  use. 

The  dietetic  treatment  is  strongly  advocated  by  Thomson 
on  the  etiologic  theory  of  a  toxemia.  It  consists  of  a  milk 
diet,  preferably  using  fermented  milks,  such  as  Koumys, 
Matzoon,  Zoolak,  etc.  Poultry,  fish,  oysters  and  eggs 
with  well  baked  or  perfectly  toasted  bread  are  to  be  used 
in  moderation;  vegetables,  such  as  asparagus,  tomatoes, 
beets,  turnips,  carrots,  spinach,  peas  and  beans,  are  pro-  ■ 
hibited,  as  well  as  red  meats ;  any  food  which  is  tasted  in 
eructations  is  to  be  avoided,  a  good  rule  to  follow  in  all 
dietetics.  Thomson's  medicinal  treatment  consists  prin- 
cipally of  intestinal  antiseptics,  mercury  being  preferred 
in  the  form  of  blue  mass  pill  once  or  twice  a  week.  I  have 
found  that  one-thirtieth  gr.  of  the  bichlorid  combined  with 
five  grs.  sodium  glycocholate-mass  three  times  a  day  after 


INCOMPLETE    BASEDOW'S   DISEASE.  229 

meals  is  more  effective;  almost  invariably  it  reduces  the 
pulse  rate,  at  the  same  time  stimulating  the  liver.  For  the 
gastric  disturbances  he  employs  resorcin,  bichromate  of 
potash,  bismuth,  salol,  etc. 

Other  drugs,  arsenic,  quinin,  strychnin,  digitalis,  iron, 
ergot,  are  all  described  as  being  indicated  and  producing 
amelioration  of  the  symptoms.  Probably  strophantus 
and  belladonna  are  the  most  reliable  of  the  empiric  treat- 
ments. On  the  theory  that  the  secretion  of  the  thyroid 
was  chemically  altered  and  that  therefore  there  was  a 
hypothyroidea,  desiccated  thyroid  and  thyroidin  have 
been  administered  with  apparent  success  in  a  few  in- 
stances, but  most  observers  report,  as  would  be  expected, 
that  the  symptoms  were  either  not  affected  or  were  aggra- 
vated under  the  treatment.  Orthophosphate  of  soda  or 
potash,  the  latter  is  to  be  preferred,  as  it  is  less  likely 
to  produce  diarrhea,  or  better  still,  phosphoric  acid  in 
full  doses,  have  produced  marked  benefit  in  many  cases, 
being  especially  advocated  by  Professor  Kocher  of  Berne. 
There  is  some  connection  between  the  phosphorus  meta- 
bolism and  the  thyroid  secretion.  Administration  of 
phosphorus  seems  to  restore  the  balance  of  the  iodin  in 
organic  combination  in  the  colloid  substance,  decreasing 
it  when  too  high  and  increasing  it  when  too  low. 

As  the  physiological  action  of  the  suprarenal  gland  is 
diametrically  opposed  to  that  of  the  thyroid  it  occurred  to 
the  writer  that  it  ought  to  at  least  relieve  the  symptoms 
due  to  the  hyperthyroidea,  further  it  had  been  shown  that 
when  the  thyroidin  molecule  is  saturated  with  iodin  it 
becomes  inert.  On  these  principles  desiccated  suprarenal 
and  Lugol's  solution  were  administered  in  a  very  marked 
case  in  1898  with  complete  success;  in  1899  Dr.  Todd 
treated  a  case  in  the  same  manner  with  success,  since  which 
date  Dr.  E.  L.  Whitney  and  others  have  tried  the  treat- 
ment in  several  cases  and  the  majority  have  done  well. 


230  THE    THYEOID    AND    PAEATHYROID    GLANDS. 

Occasionally  the  addition  of  a  little  strychnia  has  mate- 
rially assisted  the  heart  symptoms.  This  treatment  seems 
to  give  the  best  results  in  those  cases  which  occur  at  pu- 
berty, menstruation  or  during  and  after  pregnancy,  and  in 
the  atypical  cases  referred  to  above  phosphoric  acid  com- 
bined with  this  treatment  has  also  apparently  been  of  use. 

Electricity  has  been  strongly  advocated  by  M.  Vig- 
oroux  and  others.  He  recommends  that  the  constant  cur- 
rent should  be  applied  to  the  neck  and  the  interrupted 
current  to  the  precordial  region.  In  using  the  constant 
current  the  electrodes  should  be  firmly  pressed  deep  into 
the  neck  beneath  the  angle  of  the  jaw  at  each  side  for 
about  seven  minutes  or  until  the  skin  is  slightly  red.  The 
strength  of  the  Faradic  current  depends  upon  the  sensa- 
tions of  the  patient,  bearing  in  mind  that  they  are  in  a 
nervous  and  excitable  condition. 

In  the  most  severe  cases  medical  treatment  fails  and 
recourse  has  to  be  made  to  the  surgeon.  Ligation  of  the 
thyroid  arteries  and  partial  removal  of  the  gland  is  at- 
tended with  considerable  success,  the  mortality  being 
about  1  per  cent  or  less.  In  cases  where  the  exophthalmos 
is  the  most  severe  symptom,  section  of  the  cervical  sympa- 
thetic is  said  to  be  followed  by  good  results. 

Some  observers  have  claimed  that  thymus  feeding  has 
produced  good  results  in  some  cases.  It  seems  hardly 
probable,  however,  that  feeding  with  a  gland  which  should 
have  atrophied  under  normal  conditions  and  which  is  path- 
ologically persistent  in  the  majority  of  severe  cases  should 
produce  any  good  effects. 

Eecently  attempts  have  been  made  to  treat  Basedow's 
disease  by  means  of  a  serum  but  with  only  very  partial 
success.  Portis  endeavored  to  produce  symptoms  similar 
to  those  which  follow  removal  of  the  thyroid  and  para- 
thyroid glands  in  animals  by  means  of  specific  cytotoxins 


INCOMPLETE    BASEDOW'S   DISEASE.  231 

whose  action  was  selective  on  the  thyroid  and  parathyroid 
cells,  producing  degeneration  and  loss  of  function.  Min- 
kovsky and  Goutscharukov  claim  they  have  made  a  thyro- 
toxic serum  which  produced  symptoms  resembling  tetany, 
the  thyroid  cells  showing  evidence  of  degeneration.  Min- 
kovsky introduced  the  thyroid  glands  of  dogs  into  the  peri- 
toneal cavity  of  cats  at  fourteen  day  intervals;  after  the 
third  injection  the  serum  was  separated  and  proved  toxic 
to  dogs.  Goutscharukov  used  the  thyroids  of  dogs,  inject- 
ing them  into  rams,  producing  a  serum  which  was  thyro- 
toxic. Portis  employed  emulsions  of  dogs '  thyroids ;  be- 
ginning with  one  gland  he  increased  the  dose  to  ten  glands 
which  he  injected  into  the  peritoneal  cavity  of  a  goat.  He 
claimed  that  the  serum  of  the  injected  animal  acquired 
certain  characteristics.  Injected  into  dogs  it  produced  de- 
pression, convulsions,  vomiting,  rapid  breathing,  hemo- 
globinuria and  death ;  in  other  cases  fever,  lachrymation, 
emaciation  and  progressive  loss  of  weight.  The  thyroid 
showed  absence  of  colloid  substances,  desquamation  and 
disintegration  of  the  epithelial  cells,  followed  by  the  de- 
velopment of  papillary  proliferations;  there  were  degen- 
erative changes  in  other  organs.  Moebius,  assuming  that 
the  blood  of  thyroidectomized  animals  would  contain  cer- 
tain bodies  which  would  normally  have  been  destroyed  by 
the  thyroid  secretion,  considered  that  they  might  be  used 
to  neutralize  the  excess  of  thyroid  secretion  in  Basedow's 
disease.  Lanz  employed  the  milk  from  thyroidectomized 
goats  in  several  cases  with  good  results.  Moebius  serum 
was  prepared  by  Merck  and  used  with  satisfactory  results 
by  J.  Moebius  and  Schultes,  but  Murray  was  unable  to 
obtain  any  results. 

Dr.  Murray  of  Newcastle-upon-Tyne  prepared  a  serum 
by  feeding  rabbits  on  gradually  increasing  doses  of  thyroid 
extract,  but  obtained  no  definite  results.     Lepine  prepared 


THE    THYROID    AND    PARATHYROID    GLANDS, 

a  serum  in  a  similar  way  by  feeding  a  goat  on  sheep 
thyroids. 

One  or  two  cases  have  been  reported  where  parathyroid 
feeding  produced  good  results,  but  further  experiments 
are  necessary  before  definite  conclusions  can  be  reached 
on  this  point. 


CHAPTER    XIV. 

THYROID  FEEDING  IN  GENERAL  THERAPEUTICS. 

The  thyroid  has  an  especial  therapeutic  action  which 
can  be  utilized  to  advantage  even  when  there  is  no  defi- 
ciency in  the  secretion  of  the  gland  of  the  patient.  As 
shown  in  a  previous  chapter,  its  administration  dilates  the 
arteries,  reducing  the  blood  pressure,  thereby  accelerating 
the  heart 's  action  and  decreasing  the  work  of  that  organ ; 
it  also  increases  metabolism,  causing  an  increased  elimina- 
tion of  nitrogen  as  well  as  of  carbon  dioxid ;  it  also  acts  as 
a  diaphoretic  by  dilatation  of  the  vessels  of  the  skin ;  is  a 
slight  diuretic  and  increases  the  oxygen  carrying  power  of 
the  blood.  Probably  its  primary  actions  are  the  dilatation 
of  the  vessels  and  the  increased  oxidation. 

The  use  of  thyroid  as  an  accessory  to  other  treatments 
is  perfectly  rational,  especially  in  cases  where  there  is  high 
arterial  tension  with  increased  mean  pressure :  the  vasodi- 
lators of  the  Pharmacopeia  are  too  fugitive  in  their  action 
to  be  of  much  value  except  in  emergency,  but  in  the  thy- 
roid we  have  a  drug  which  can  be  administered  for  any 
length  of  time  and  which  is  the  natural  drug,  so  to  speak, 
of  the  body. 

One  point  in  the  physiological  action  of  thyroid  and 
in  which  it  acts  differently  to  the  nitrites  is  its  effect  on 
the  capillary  circulation.  The  nitrates  appear  to  dilate  the 
arterioles,  thereby  increasing  the  heart  rate,  but  they  do 
not  produce  an  increased  bulk  of  blood  in  the  peripheral 
circulation.  The  administration  of  thyroid  appears  to 
dilate  the  capillaries  at  least  of  the  skin,  producing  marked 
reddening  and  diaphoresis;  this  point  is  further  empha- 
sized by  the  dry  harsh  condition  of  the  skin  in  hypothy- 

233 


THE    THYROID    AND    PARATHYROID    GLANDS. 

roidea.  The  thyroid  is  the  only  drug  in  the  writer's  ex- 
perience which  acts  as  a  capillary  dilator;  the  Nauhehn 
baths  have  the  same  effect,  with  this  advantage,  that  at 
the  same  time  the  pulse  rate  goes  down. 

When  the  first  successes  were  recorded  thyroid  was  util- 
ized in  almost  every  kind  of  disease  without  any  attention 
being  paid  to  its  indications  and  limitations ;  it  appeared 
as  if  the  dream  of  a  universal  medicine  was  about  to  be 
realized.  The  medical  literature  of  the  nineties  abounds 
in  reports  of  its  successful  use  in  albuminuria,  epilepsy, 
diseases  of  the  skin,  gout,  tuberculosis,  the  fevers,  leprosy, 
etc.,  but  whatever  good  effects  were  obtained  were  due 
either  to  the  cases  being  atypical  myxedema  or  to  the 
beneficial  effects  of  its  physiological  action,  as  stated 
above,  upon  the  patient. 

OBESITY. 

There  is  a  form  of  obesity  which  seems  to  be  due  to  a 
loss  of  function  of  the  thyroid  gland  and  which  shows  but 
few  symptoms  of  myxedema.  They  are  generally  cases 
where  there  has  been  a  somewhat  sudden  increase  of 
adipose  deposit  over  the  whole  body  following  some  acute 
disease,  such  as  typhoid  fever,  or  in  women  after  preg- 
nancy, or  when  the  climacteric  has  arrived  at  35  or  40  years 
of  age.  These  patients  will  usually  complain  of  rheumatic 
pains  in  the  limbs,  which  they  ascribe  to  the  extra  amount 
of  weight  they  have  to  cany.  There  are  also  often  ner- 
vous disturbances  which  may  be  due  to  fatty  heart,  con- 
sisting of  giddiness  and  faintness  combined  with  a  nervous 
condition  which  simulates  hysteria.  Nervous  attacks  of 
this  nature  occur  at  irregular  intervals  without  any  appar- 
ent cause,  the  patient  may  be  domineering  and  irritable, 
causing  family  troubles.  There  are  few  physical  signs 
except  the  obesity  which  may  be  confined  to  the  face  and 
body,  the  lower  limbs  being  but  little  larger  than  normal. 


GLYCOSURIA. 


235 


There  is  a  peculiar  change  in  the  contour  of  the  neck, 
which  appears  square,  the  anterior  central  portion  failing 
to  project.  Occasionally  the  symptoms  of  myxedema 
may  be  present  in  an  attenuated  form,  at  other  times  they 
are  entirely  absent. 

In  these  cases  great  care  should  be  exercised  in  the  ad- 
ministration of  the  thyroid;  on  no  account  should  more 
than  one  grain  per  day  be  given  at  the  commencement, 
increasing  the  quantity  very  slowly  and  keeping  the  pa- 
tient under  close  observation.  It  is  well  to  give  a  little 
arsenious  acid  and  strychnia  or  adonis  vernalis  at  the  same 
time.  Very  serious  accidents  may  occur  from  an  overdose 
of  the  thyroid  in  these  cases,  owing  to  the  condition  of  the 
heart  and  the  anemia  of  bulk  which  exists  in  the  obese. 
It  has  been  shown  that  in  the  moderately  obese  the  total 
weight  of  blood  in  circulation  may  be  as  low  as  one-thirty- 
third  of  the  body  weight,  when  it  is  obvious  that  any  dila- 
tation of  the  vessels  may  produce  very  serious  collapse. 
Constipation  is  often  a  very  troublesome  accompaniment 
of  obesity,  but  if  the  disease  is  due  to  thyroid  insufficiency 
the  first  sign  that  the  thyroid  treatment  is  indicated  will 
be  the  regulation  of  the  bowels. 

Thyroid  feeding  is  not  an  ' '  antif at ' '  of  universal  appli- 
cation and  should  always  be  given  with  caution.  It  is  true 
that  if  large  enough  doses  are  given  any  patient  will  lose 
flesh,  but  the  heart  failure  and  depression  of  spirits  result- 
ing prevent  its  use. 

GLYCOSURIA. 

The  increased  metabolism  of  carbohydrates  and  fats  pro- 
duced by  the  administration  of  thyroid  naturally  suggested 
its  use  in  glycosuria.  At  the  suggestion  of  Dr.  E.  L. 
Whitney  it  was  administered  to  several  patients  who  had 
sugar  in  their  urine,  and  where  possible,  prescribing  a 
mild  diabetic  diet,  viz:  the  patient  to  abstain  from  all 


236  THE    THYK0ID    AND    PAEATHYEOID    GLANDS. 

starchy  foods  and  sugars,  substituting  as  much  fat,  in  the 
shape  of  oil,  butter,  cream,  fat  meat,  etc.,  as  possible,  but 
allowing  one  slice  of  toasted  bread  twice  or  three  times  a 
day.  It  is  an  easy  matter  to  prescribe  a  diet  but  a  very 
difficult  thing  to  get  a  patient  to  keep  to  it,  but  it  was 
found  that  by  allowing  this  small  amount  of  bread  the 
patient  was  able  to  keep  to  the  diet  without  much  discom- 
fort. There  are  probably  several  forms  of  glycosuria, 
nervous,  muscular,  hepatic,  pancreatic  and  possibly  renal. 
The  thyroid  treatment  could  presumably  only  be  indicated 
in  the  hepatic  and  muscular  forms,  while  general  improve- 
ment of  the  metabolism  might  be  successful  in  the  nervous 
form.  In  the  pancreatic  form,  although  I  have  never  tried 
it,  I  should  consider  it  as  contraindicated. 

In  cases  of  glycosuria  occurring  in  old  age,  obesity,  as 
well  as  in  some  of  those  occurring  in  middle  life,  the  above 
diet,  coupled  with  the  administration  of  two  grains  of 
desiccated  thyroid  and  five  grains  of  sodium  glycocholate- 
mass  (Hynson  &  Westcott,  Baltimore),  to  increase  the  ab- 
sorption of  fat  and  to  purge  the  liver,  have  brought  about 
complete  recovery  in  several  cases,  so  that  on  returning  to 
their  ordinary  diet  there  was  no  return  of  the  glycosuria. 
In  other  cases  in  which  the  diagnosis  of  hepatic  glycosuria 
was  made  the  treatment  failed,  though  in  most  cases  there 
was  an  improvement  in  the  general  condition  of  the  pa- 
tient which  was  probably  due  more  to  the  diet  than  to  the 
drugs. 

SENILISM. 

In  old  age  the  thyroid  atrophies  under  normal  condi- 
tions and  although  the  administration  of  thyroid  will  not 
restore  youth,  it  will,  if  given  in  small  doses  with  some 
stimulant,  such  as  opium  or  strychnin  and  arsenious  acid, 
improve  the  action  of  the  heart  and  dilate  the  vessels, 
increasing  the  bulk  of  the  circulation  to  the  various  organs. 
In   senilism   it  must  be   administered  with   caution,   as 


EPILEPSY.  237 

atheroma  of  the  arteries  or  fatty  degeneration  of  the  heart 
muscle  may  exist. 

beight's  disease. 

In  the  early  stages  of  this  disease,  when  the  headaches, 
the  dizziness  and  the  dilatation  of  the  left  ventricle  have 
commenced,  all  of  which  symptoms  are  primarily  due  to 
increased  mean  blood  pressure,  thyroid  will  often  relieve 
the  symptoms  and  arrest  the  disease  in  its  progress.  The 
highest  mean  blood  pressure  the  writer  ever  found,  215 
mm.  Hg.,  was  in  a  man  of  59  years  of  age,  who  complained 
of  the  most  agonizing  paroxysms  of  pains  in  the  head  and 
limbs  and  who  had  an  apex  beat  to  the  left  of  the  nipple,  a 
slight  trace  of  albumin  in  his  urine  with  other  symptoms 
of  early  Bright 's.  He  was  relieved  by  thyroid  treatment 
and  up  to  the  present  the  disease  does  not  appear  to  have 
progressed.  Many  cases  can  be  relieved  and  the  progress 
of  the  disease  arrested  by  using  the  thyroid  as  a  means  of 
reducing  the  blood  pressure  and  attending  to  the  digestive 
organs  and  the  intestinal  tract. 

EPILEPSY. 

It  would  seem  that  thyroid  treatment  would  be  indi- 
cated in  epilepsy,  as  the  contraction  of  the  vessels  is  the 
immediate  cause  of  the  spasm,  but  experience  has  shown 
that  not  only  does  the  treatment  do  no  good  but  is  posi- 
tively harmful,  increasing  the  number  and  severity  of  the 
spasms.  There  have  been  a  few  cases  recorded  where  the 
administration  of  thyroid  appears  to  have  relieved  and 
even  cured  but  they  are  rare.  Parathyroid  feeding  would 
be  presumably  indicated  from  the  results  of  the  physio- 
logical experiments  detailed  in  a  previous  chapter,  and 
Dr.  Charles  G.  Hill  gave  thyroid  and  parathyroid  to  an 
idiotic  epileptic  child  in  Mount  Hope  Ketreat.  The  child 
improved  in  mentality  and  grew  considerably,  he  also  be- 
came clean  in  his  habits,  his  seizures  were  less  frequent 


238  THE    THYKOID    AND    PARATHYROID    GLANDS. 

and  much  less  severe,  but  whether  this  latter  was  due  to 
the  parathyroids  or  to  his  general  improvement  it  is  diffi- 
cult to  say.  In  another  case  of  epilepsy  in  a  young  man 
the  parathyroids  were  given  alone  with  very  great  im- 
provement, the  seizures  being  reduced  from  one  or  two 
a  week  to  one  or  two  in  three  months.  In  a  third  case 
Dr.  Hill  reports  decided  improvement.  -These  results  are 
sufficiently  satisfactory  to  call  for  a  further  trial  of  the 
drug. 

MENSTRUAL   DISTURBANCES. 

From  the  connection  of  the  thyroid  with  the  organs  of 
generation  it  is  in  this  field  that  the  most  beneficial  results 
should  be  expected ;  probably  no  drug  is  of  so  universal  a 
benefit  in  menstrual  disorders  as  the  thyroid.  At  puberty,, 
when  menstruation  is  delayed,  irregular  or  scanty,  a  small 
dose  of  thyroid  daily  for  a  month  or  two  will  often  bring 
about  a  normal  menstruation  with  improvement  of  the 
general  health.  In  young  women  who  suffer  from  amen- 
orrhea or  dysmenorrhea  the  same  treatment  is  usually 
effective  and  should  always  be  tried  before  the  patient  is 
condemned  to  a  surgical  operation.  It  should  be  remem- 
bered, in  examining  these  cases,  that  many  of  the  acute 
diseases  of  childhood  produce  a  sclerosis  and  consequent 
loss  of  function  of  the  thyroid  gland,  which  may  render 
it  incapable  of  developing  sufficiently  at  puberty  for  the 
increased  call  upon  its  functionation.  The  thyroid,  as  was 
•  stated  in  the  chapter  on  Physiology,  increases  in  size 
prior  to  puberty  and  enlarges  at  every  menstruation  as 
well  as  during  pregnancy,  and  it  is  therefore  evident  that 
its  functionation  acts  as  a  stimulating  cause  to  the  sexual 
processes.  In  cases  of  grown  women,  and  especially  those 
who  have  not  been  married,  it  often  happens,  though  no 
atrophy  of  the  gland  can  be  detected,  that  the  stimulus  of 
an  extra  amount  of  thyroid  secretion  given  as  desiccated 
thvroid  will  reestablish  menstruation.     At  the  climacteric,. 


TETANY.  239 

especially  when  occurring  prematurely,  the  drug  is  often 
of  benefit,  sometimes  reestablishing  menstruation  for  a 
time  and  relieving  the  various  minor  symptoms  which  are 
so  common  at  this  period. 

Dr.  Charles  Gr.  Hill,  of  Mount  Hope  Retreat,  was  the 
first  to  observe  this  very  important  result  of  thyroid  feed- 
ing. He  noticed  that  in  some  of  the  chronic  insane  who 
had  not  menstruated  for  a  year  or  two  there  was  a  return 
of  the  flow  after  one  or  two  months '  treatment,  invariably 
causing  improvement  in  their  physical  and  mental  condi- 
tion. For  some  reason,  which  is  at  present  inexplicable, 
the  administration  of  parotid  gland  is  said  to  have  a  bene- 
ficial effect  upon  some  cases  of  dysmenorrhea  and  is  at 
times  combined  with  thyroid  treatment.  It  must  be  re- 
membered that  unlike  other  emmenagogues  which  can  be 
administered  in  large  doses,  producing  their  effects  in  a 
day  or  two,  thyroid  must  be  given  daily  for  a  month, 
doubling  the  dose  for  a  day  or  two  before  menstruation  is 
due,  and  it  may  take  two  or  more  months  before  the  end 
is  attained.  In  many  cases  which  had  been  diagnosed  as 
retroflexion  of  the  uterus  by  gynecologists  and  upon  whom 
they  had  operated  without  giving  relief,  a  course  of  thy- 
roid treatment  has  brought  about  normal  functionation 
and  perfect  health. 

TETANY. 

Tetany  is  produced  by  thyroidectomy  and  occasionally 
occurs  as  a  symptom  in  cachexia  strumipriva,  showing 
that  it  can  be  produced  by  cessation  of  function  of  the 
thyroid  and  parathyroid  glands;  certain  experiments  de- 
tailed in  a  previous  chapter  seem  to  point  to  the  latter  be- 
ing the  etiologic  factor.  In  those  cases  of  cachexia  strumi- 
priva which  survive  the  tetanic  symptoms  may  disappear 
for  a  shorter  or  longer  period,  reappearing  during  preg- 
nancy or  some  other  excitant. 

Tetany  is  usually  associated  with  disturbances  of  the 


240  THE    THYROID    AND    PARATHYROID    GLANDS. 

digestive  tract  and  is  probably  due  to  a  toxemia;  it  has 
also  been  known  to  occur  as  an  epidemic.  Emotions, 
muscular  effort,  dentition  and  rachitis  are  all  given  as 
exciting  causes.  It  occasionally  occurs  in  Basedow's  dis- 
ease. Infancy,  puberty,  menstruation,  lactation  and  preg- 
nancy are  the  periods  at  which  it  most  commonly  occurs. 
The  disease  has  been  recorded  as  associated  with  gout, 
rheumatism  and  malaria. 

There  are  certain  forms  of  epilepsy  which  have  been 
described  as  "tetanoid  epilepsy, "  in  which  there  are  only 
tonic  contractions.  The  head  may  be  turned,  the  arms 
extended,  elbow  joints  flexed  and  fingers  flexed,  the  latter 
in  the  interosseal  position.  The  spasm  may  last  for  a 
longer  or  shorter  time,  the  muscles  affected  varying,  there 
may  be  frothing  at  the  mouth  and  the  tongue  may  be  bit- 
ten, the  distinctive  point  being  that  there  are  no  clonic 
convulsions  as  in  the  true  epileptic  seizure. 

In  certain  cases  in  childhood  the  tetany  may  be  due  to 
defective  thyroid  secretion,  cases  being  on  record  where 
thyroid  treatment  has  proved  effective.  The  physician 
often  never  sees  the  patient  during  the  seizure  and  has  to 
be  content  with  the  report  of  the  friends  as  to  the  nature 
of  the  convulsions.  Consequently  he  is  unable  to  make 
the  distinction  between  a  tetanoid  and  a  true  epileptic 
seizure.  Though  by  far  the  greater  number  of  convul- 
sions in  childhood  are  due  to  digestive  disturbances,  it  is 
a  point  worthy  of  careful  investigation,  especially  if  the 
attacks  occur  at  intervals,  as  to  whether  the  attacks  are 
epileptic  or  tetanic  in  their  nature  and  in  the  latter  case 
to  examine  for  possible  hypothyroidea. 

The  importance  of  the  thyroid  during  menstruation, 
pregnancy  and  lactation  has  been  emphasized  in  preceding 
chapters,  and  convulsions  occurring  at  these  periods  with- 
out any  apparent  cause  point  to  thyroid  insufficiency. 
Attacks  occurring  during  pregnancy,  labor  or  lactation 


ECLAMPSIA.  24] 

are  usually  termed  eclamptic.  Recent  investigations  go 
to  prove  that  eclampsia  is  due  to  thyroid  insufficiency  in 
a  certain  number  of  cases.  There  are  cases  where  convul- 
sions occur  during  the  latter  months  of  pregnancy  as  well 
as  during  labor,  which  continue  at  intervals  without  these 
exciting  causes. 

A  case  occurred  in  the  writer's  practice  where  a  mar- 
ried woman  had  had  convulsions  during  pregnancy  and 
labor  on  three  occasions,  giving  birth  to  healthy  children. 
During  the  fourth  pregnancy  and  labor  no  convulsions  oc- 
curred ;  with  the  fifth  and  last  pregnancy  there  were  again 
convulsions.  On  recovery  the  seizures  returned  at  inter- 
vals, sometimes  as  often  as  two  or  three  times  per  week. 
The  convulsion  consisted  in  tonic  contractions  only,  the 
patient  being  partially  conscious  during  the  attack.  She 
was  treated  with  large  doses  of  thyroid,  as  high  as  30  grs. 
per  diem;  the  seizures  were  reduced  in  number  and  se- 
verity but  after  treatment  was  suspended  they  gradually 
increased  in  number  and  severity,  again  decreasing  on  the 
resumption  of  treatment. 

From  experimental  and  clinical  evidence  it  is  probable 
that  a  certain  number  of  cases  of  tetany  which  simulate 
epilepsy  are  due  to  thyroid  insufficiency. 

ECLAMPSIA. 

The  consensus  of  opinion  at  present  is  that  eclamptic 
convulsions  are  the  result  of  an  autointoxication,  and  that 
the  conditions  existing  are  an  increased  mean  blood  pres- 
sure, a  perverted  metabolism,  a  decreased  elimination  by 
the  kidneys,  with,  in  the  majority  of  cases,  albuminuria 
with  or  without  casts,  the  pathologic  findings  being  fatty 
degeneration  of  the  liver  and  kidneys.  The  placenta  may 
be  looked  upon  as  a  digestive  organ  preparing  the  nutri- 
tion for  the  fetus,  and  possibly  it  may  also  have  a  hepatic 
function  destroying  the  toxic  products  of  fetal  metabolism 

16 


242  THE    THYROID    AND    PARATHYROID    GLANDS. 

before  the  fetal  blood  enters  the  vena  cava ;  consequently 
a  pathologic  condition  of  the  placenta  might  produce 
toxemia  in  the  mother. 

The  connection  of  the  thyroid  gland  with  the  organs  of 
generation  has  been  well  established,  the  gland  enlarging 
at  puberty  and  during  menstruation,  pregnancy  and  lacta- 
tion. The  far-reaching  effect  of  hyposecretion  of  the  gland 
and  the  various  disturbances  the  condition  produces  has 
led  many  investigators  to  experiment  as  to  the  possibility 
of  producing  eclampsia  by  partial  thyroidectomy. 

In  experimenting  with  thyroidectomy  Halstead  observed 
that  a  bitch,  who  had  been  deprived  of  a  large  portion  of 
her  thyroid  gland  but  remained  in  apparently  perfect 
health,  became  impregnated  by  a  normal  dog  and  prog- 
ressed without  any  signs  of  hypothyroidea  till  term,  but 
at  delivery  showed  all  the  symptoms  of  athyroidea,  in- 
cluding convulsions.  Since  this  observation  many  experi- 
ments have  been  made  on  this  point,  notably  those  of  Ver- 
straeter  and  Vanderlinden  (Ann.  de  la  Soc.  de  Med.  de 
Gand.,  1897),  v.  Eiselberg  (Die  Krankheiten  der  Schil- 
druse),  I.  Jeandelize  (Insuffisance  thyroidienne  et  para- 
thyroidienne)  and  Lange  (Zeit.  f.  Geburt.  u.  Gyn.). 

The  latter  removed  one-fifth  of  the  thyroid  gland  from 
10  pregnant  cats;  2  died  in  coma,  one  23  days  and  the 
other  38  days  after  the  operation,  3  had  convulsions  23 
and  25  days  after  operation.  Three  of  these  cases  had 
albuminuria  and  at  autopsy  fatty  degeneration  of  the  liver 
and  kidneys  was  found.  The  other  five  cats  remained  well, 
but  at  autopsy  three  of  them  were  found  to  have  the  same 
pathologic  lesions.  Lange  also  examined  a  series  of  133 
cases  of  pregnancy  and  found  that  the  hypertrophy  of  the 
thyroid  commenced  in  the  fifth  month  in  multiparas  and 
in  the  sixth  month  in  primiparas;  he  also  found  on  the 
administration  of  small  doses  of  thyroid  to  pregnant 
women  with  enlarged  thyroids  that  the  gland  returned  to 


ECLAMPSIA. 


243 


normal  size,  but  on  the  cessation  of  the  treatment  it  again 
hypertrophied.  Of  the  133  cases  examined  he  found  the 
gland  enlarged  in  108  cases,  3  were  doubtful,  in  22  there 
was  no  enlargement,  of  the  22  twenty  showed  albuminuria, 
16  albuminuria  with  casts,  6  of  these  cases  developed 
eclampsia ;  of  the  108  with  hypertrophied  gland  only  two 
had  albuminuria  and  one  of  these  was  a  nephritic ;  none  of 
the  108  developed  eclampsia. 

Herrgott  reports  a  case  of  incomplete  myxedema  where 
eclampsia  developed.  Verstraeter,  Vanderlinden  and 
Nicholson  (The  Scot.  Med.  and  Surg.  Jour.,  1901)  report 
cases  of  eclampsia,  which  they  attribute  to  thyroid  insuf- 
ficiency, the  latter  treating  a  case  with  thyroid  with  suc- 
cess. 

The  thyroid  function  being  increased  during  pregnancy 
it  is  evident  that  if  for  any  reason  the  thyroid  has  failed 
to  fully  develop,  though  secreting  sufficient  under  ordinary 
conditions,  it  will  fail  to  respond  to  the  excessive  demand 
upon  it  during  pregnancy.  It  is  by  no  means  uncommon 
for  the  thyroid  to  be  affected  by  the  acute  diseases  of 
childhood,  rheumatism,  typhoid,  etc.,  as  has  been  shown 
by  Gamier  and  Roger ;  consequently  at  the  first  pregnancy 
there  is  a  deficiency  of  thyroid  secretion  which  may  be  a 
factor  in  producing  eclamptic  convulsions  at  term  in  pri- 
miparas.  The  excitation  of  the  gland  during  pregnancy 
will  have  a  tendency  to  increase  its  functionation,  prevent- 
ing the  recurrence  of  the  symptoms  at  the  next  pregnancy. 
In  other  cases  the  gland  never  acquires  a  sufficient  secret- 
ing power  and  eclamptic  convulsions  occur  at  every  suc- 
cessive labor.  In  those  who  have  no  eclamptic  symptoms 
at  the  first  pregnancy,  but  in  whom  they  appear  in  the 
later  pregnancies,  it  may  be  assumed  that  the  strain  upon 
the  gland  during  the  first  pregnancy  or  some  intercurrent 
disease  has  affected  the  functionation  of  the  gland. 

The  principal  symptoms  of  eclampsia  are  the  same  as 


244  THE    THYEOID    AND    PAKATHYKOID    GLANDS. 

those  t»f  hypothyroidea,  viz :  high  mean  arterial  pressure, 
decreased  elimination  by  the  kidneys,  perverted  metabo- 
lism and  very  often  albumin  and  casts.  In  partially  thy- 
roidectomized  animals  the  same  symptoms  occur  while  the 
principal  pathologic  lesion  is  fatty  degeneration  of  the 
liver  and  kidneys.  From  the  above  data  it  is  probable 
that  a  certain  number  of  cases  of  eclampsia  are  due  to  a 
hyposecretion  of  the  thyroid  and  parathyroid  glands. 

The  following  case  occurred  in  the  practice  of  Dr. 
Charles  G.  Hill: 

A  primipara  was  examined  six  weeks  before  term.  Her 
24  hours'  urine  was  found  to  contain  11.37  grms.  albumin, 
with  some  casts,  the  nitrogen  occurring  as  urea,  79.8  per 
cent ;  ammonia  N,  9.2  per  cent ;  uric  acid  N,  1.8  per  cent ; 
residual,  9.2  per  cent;  chlorids,  10.4;  phosphoric  acid, 
P205,  2.65: 

carbon        G.1G 

-=0.77. 
nitrogen    7.08 

The  blood  pressure  showed  a  very  high  mean  in  proportion 
to  the  maximum 

mean    108  mm.  Hg. 

:0.8, 


max.     208  mm.  Hg. 


with  a  pulse  of  105.  Dr.  Hill,  who  had  attended  her  be- 
fore marriage,  had  diagnosed  hypothyroidea  when  she  had 
improved  under  thyroid  treatment.  He  gave  her  full 
doses  of  thyroid  and  parathyroid,  the  blood  pressure  fall- 
ing under  the  treatment  to 

mean  152  mm.  Hg. 

0.76; 


max.    198  mm.  Hg. 


pulse,  95 ;  the  relation  of  maximum  pressure  to  mean  pres- 
sure being  nearly  normal.  She  was  delivered  two  weeks 
before  term  without  any  accident.  The  day  after  delivery 
the  blood  pressures  were 


IMPOTENCE.  245 

mean    140  mm.  Hg. 


max.      182  mm.  Hg. 


=  0.7 


or  normal.  Nineteen  days  after  delivery  albumin  was 
absent  from  the  urine ;  urea  N,  83.7  per  cent ;  ammonia  N, 
8.0  per  cent;  uric  acid  N,  0.55  per  cent;  residual  N,  7.75 
per  cent,  being  normal  except  for  the  still  high  proportion 
of  ammonia  N : 

carbon       4.56 

=  1.0; 

nitrogen    4.48 

chlorid,  6.4;  phosphoric  acid,  P205,  1.68.  The  thyroid 
treatment  was  discontinued  at  the  time  of  delivery,  but 
commenced  again  on  the  fourth  day,  as  the  urine  became 
scanty,  the  pulse  hard  and  lactation  had  not  commenced. 
In  a  day  or  two  the  lactation  was  normal,  the  patient 
making  an  uninterrupted  recovery. 

IMPOTENCE. 

Impotence  in  man  and  frigidity  in  woman  are  conditions 
which  are  occasionally  benefited  by  thyroid  treatment.  In 
man  when  the  want  of  sexual  power  is  due  to  a  non- 
development  of  the  penis,  as  shown  by  the  small  size  of 
the  organ  with  an  elongated  prepuce  covering  the  glans 
which  is  with  difficulty  withdrawn,  and  when  the  testicles 
are  small  and  soft  to  the  touch,  the  scrotum  without  the 
pigmentation  and  the  rugae  of  the  normal  adult,  combined 
with  a  history  of  congenital  want  of  power  and  possibly 
also  of  desire,  a  course  of  thyroid  feeding,  extending  over 
several  months,  will  sometimes  produce  a  marked  develop- 
ment of  the  penis,  the  prepuce  withdrawing  from  the  glans, 
the  testicles  enlarging  and  becoming  firm  to  the  touch 
and  the  scrotum  normal  in  appearance.  The  desire  and 
capability  for  the  sexual  act  may  become  normal  and  even 
excessive.  I  have  often  observed  among  the  insane  that 
patients  under  thyroid  treatment  became  intensely  erotic, 


246  THE    THYEOID    AND    PARATHYROID    GLANDS. 

masturbating  continually.  This  is  more  often  observed  in 
females.  Occasionally  the  treatment  had  to  be  suspended 
owing  to  the  sexual  excitement  it  produced.  If  the  im- 
potence is  due  to  pollutions  or  spermatorrhea  or  any 
derangement  of  the  circulation  of  the  organs,  thyroid 
treatment  is,  of  course,  useless,  but  in  those  cases  where 
there  is  no  apparent  cause  and  especially  when  the  patient 
is  obese  the  treatment  is  often  successful.  In  the  female 
it  is  difficult  to  diagnose  arrested  development  of  the 
sexual  organs,  but  should  there  be  a  history  of  delayed 
menstruation  with  a  tendency  to  masculinism  the  treat- 
ment will  often  increase  the  sexual  desire. 

In  cryptorchidia,  either  unilateral  or  bilateral,  thyroid 
feeding  will  sometimes  cause  the  descent  of  the  testes. 

It  is  obvious  that  this  treatment  is  only  indicated  in 
isolated  cases  where  there  is  evidence  of  arrested  develop- 
ment of  the  organs  or  loss  of  thyroid  function.  A  female 
patient,  who  was  under  thyroid  treatment  for  amenorrhea 
and  delusions,  complained  of  almost  uncontrollable  sexual 
desire  after  the  menstruation  had  been  established  and  the 
delusions  had  disappeared. 

From  the  connection  of  the  thyroid  with  the  sexual 
organs,  its  increase  in  size  at  puberty,  during  menstrua- 
tion and  pregnancy,  as  well  as  from  the  fact  that  in  cretin- 
ism and  infantilism  the  genitalia  do  not  develop  and 
puberty  is  either  never  established  or  delayed  for  it  may 
be  years,  it  is  surprising  that  more  cases  of  impotence  in 
the  male  and  frigidity  in  the  female  are  not  benefited  by 
thyroid  treatment. 

NERVOUS   DISEASES. 

As  has  already  been  stated  the  action  of  the  thyroid  is 
alterative.  By  dilating  the  vessels  it  brings  an  increased 
blood  supply  to  the  organs  and  tissues  of  the  body  and 
consequently  may  and  does  act  beneficially  in  many  dis- 


DISEASES    OF    THE    SKIX.  247 

eases.  In  most  cases  where  there  is  an  increased  mean 
blood  pressure  thyroid  medication  will  do  good,  provided 
it  is  not  pushed  so  far  as  to  produce  thyroidismus  or  men- 
tal depression  from  its  effect  upon  the  heart.  In  some  of 
these  unclassified  conditions  which  are  grouped  in  the 
conglomeration  of  "functional  neuroses"  it  will  be  found 
on  careful  examination  that  there  are  symptoms  of  incom- 
plete or  marked  myxedema,  while  in  others  the  increased 
mean  pressure  is  an  indication  for  thyroid  treatment. 

PABALYSIS    AGITAXS  —  PAEKIXSOX 's    DISEASE. 

This  disease  is  ascribed  to  exogenous  toxemia  from  al- 
cohol, lead,  mercury,  etc.,  but  variability  and  the  absence 
of  nerve  lesions  seems  to  jDoint  to  some  constitutional  de- 
fect or  to  autotoxemia.  Castelloi  considers  that  autoin- 
toxication is  the  etiologic  factor.  The  tremblings,  sensa- 
tions of  heat  and  other  symptoms  common  in  this  disease 
also  occur  in  exophthalmic  goitre,  which  led  him  to  think 
that  the  thyroid  might  be  implicated.  In  two  post-mor- 
tems he  found  in  the  first  that  the  thyroid  only  weighed 
145  grains  and  in  the  second  the  gland  was  cystic.  He 
also  claims  to  have  had  good  results  from  thyroid  feeding. 

DISEASES    OF    THE    SKIX. 

Thyroid  treatment  has  been  found  to  be  of  benefit  in 
many  cases  of  skin  disease,  notably  psoriasis,  due  no  doubt 
to  the  increased  circulation  in  the  skin.  It  will  be  remem- 
bered that  one  of  the  most  marked  symptoms  of  myxedema 
is  connected  with  the  skin,  the  pseudoedema  and  the  dry, 
scaly,  harsh  condition,  with  the  absence  of  perspiration 
and  secretion  of  the  sebaceous  glands  show  that  the  circu- 
lation is  decreased.  It  is  probable  that  the  benefit  derived 
in  skin  diseases  from  thyroid  treatment  is  due  to  the  in- 
creased circulation  to  the  parts. 


248  THE    THYKOID   AND    PARATHYROID    GLANDS. 

ADIPOSIS   DOLOROSA. 

Of  this  rare  disease  only  five  cases  have  yet  come  to 
autopsy,  four  having  been  reported  by  Dr.  P.  X.  Dercum 
and  one  by  Dr.  Burr.  In  two,  gross  disease  of  the  thyroid 
was  found,  the  glands  being  the  seat  of  calcareous  deposit; 
in  the  third  there  was  irregular  atrophy  of  the  thyroid 
gland  with  efforts  at  compensatory  hypertrophy;  in  the 
fourth  there  were  the  same  changes  in  the  thyroid  with 
enlargement  and  gliomatous  degeneration  of  the  pituitary 
body.  In  the  fifth  case  the  changes  in  the  thyroid  were 
slight,  but  there  was  adenocarcinoma  of  the  protuberance 
of  the  pituitary  body  and  hemolymph  glands.  The  rela- 
tion of  the  thyroid  to  this  disease  seems  to  be  established, 
but  is  probably  combined  with  diseases  of  the  pituitary 
body.  Thyroid  treatment  does  not  seem  to  have  amelior- 
ated the  symptoms. 

In  akromegaly  there  seems  to  be  some  derangement  of 
the  thyroid  gland,  but  up  to  the  present  the  etiology  of  the 
disease  is  unknown. 

HEMORRHAGE. 

In  certain  cases  of  persistent  hemorrhage  the  adminis- 
tration of  thyroid  extract  in  5  gr.  doses  with  the  addition 
of  calcium  chlorid  will  increase  the  coagulative  power  of 
the  blood.  Dr.  Bloodgood  reports  cases  where  he  found 
this  treatment  effective  when  other  methods  of  arresting 
bleeding  had  failed. 

MENTAL   DISEASES. 

The  use  of  the  thyroid  in  insanity  dates  from  1892, 
when  it  was  used  in  the  Morningside  Asylum  in  Edin- 
burgh with  very  good  results,  since  which  time  it  has  been 
used  with  varying  success  by  different  specialists.  There 
has  been  unfortunately  an  idea  prevalent  that  the  treat- 
ment was  applicable  to  all  forms  of  insanity  and  it  has 


MENTAL   DISEASES.  249 

been  used  without  discrimination,  no  attention  being  paid 
to  the  symptomatic  indications  for  its  use.  Several  spe- 
cialists have  given  it  to  a  large  number  of  cases  and,  re- 
porting improvement  or  cure  in  about  5  per  cent  of  the 
cases,  were  disappointed  at  the  result.  Easterbrook  finds 
it  of  benefit  in  about  9  per  cent  of  all  cases,  but  disease  of 
the  thyroid  gland  is  said  to  be  more  prevalent  in  Scotland 
than  in  this  country.  In  the  experience  gained  at  Mount 
Hope  Retreat  I  am  of  opinion  that  about  5  per  cent  of  all 
cases  are  improved  by  the  drug  and  in  many  of  these  it  is 
only  as  an  accessory  to  other  treatment  that  it  is  of  benefit. 

The  number  of  insane  patients  suffering  from  myx- 
edema, even  in  an  atypical  form,  is  probably  very  small 
and,  as  the  mental  disturbances  may  assume  the  form  of 
dementia,  melancholia,  or  mania,  the  psychic  disturbances 
are  no  guide  to  the  therapeutic  use  of  thyroid.  It  is  very 
rare  that  it  is  of  any  use  in  the  acute  stages  of  the  disease 
and  has  the  objection  of  decreasing  the  appetite,  some- 
times producing  absolute  refusal  of  food,  and  further  a 
drug  which  increases  metabolism  and  elimination  of  both 
nitrogen  and  carbon  must  be  contraindicated  when  there 
is  poor  assimilation  and  the  system  run  down.  Before 
commencing  to  administer  thyroid  the  digestive  organs 
should  be  got  into  a  healthy  condition  and  it  is  a  good 
rule  not  to  give  thyroid  unless  the  nitrogen  elimination  is 
at  least  8  to  10  grms.  in  the  24  hours.  In  cases  of  true 
myxedema  this  does  not  apply,  as  often  in  these  cases  the 
nitrogen  is  as  low  as  5  grms.  and  rises,  the  appetite  im- 
proving at  the  same  time  on  the  administration  of  thyroid. 

The  indications  for  thyroid  treatment  are  the  same  in 
insanity  as  in  other  diseases,  the  condition  of  the  circula- 
tion being  the  principal  guide.  In  cases  of  acute  mania, 
where  the  mean  and  maximum  blood  pressure  are  low,  the 
heart  action  weak  and  the  patient  suffering  from  anemia 
of  bulk,  it  is  strongly  contraindicated  and  may  produce 


250  THE    THYROID    AND    PARATHYROID    GLANDS. 

serious  results.  Ou  the  other  hand,  in  cases  where  the 
pulse  is  full,  strong  and  rapid,  the  mean  and  maximum 
pressure  high,  the  nitrogen  elimination  15  grins,  or  even 
more,  with  a  good  appetite  and  hyperchlorhydria  of  the 
stomach,  thyroid  combined  with  opium  will  often  produce 
very  good  results,  the  thyroid  counteracting  the  contrac- 
tion of  the  abdominal  vessels  and  heart  stimulation  of  the 
opium. 

When  there  is  marked  venous  stasis,  pointing  to  insuf- 
ficiency of  the  right  heart,  and  where  the  mean  pressure  is 
normal  or  little  above  normal,  and  the  maximum  pressure 
low,  thyroid  is  contraindicated,  as  it  will  increase  the 
amount  of  blood  on  the  venous  side  of  the  circulation  by 
dilating  the  arterioles ;  on  the  contrary,  if  there  is  a  dilata- 
tion of  the  left  side  of  the  heart,  with  high  mean  pressure 
and  either  normal  or  low  maximum  pressure,  digitalis, 
strychnin  or  adonis  vernalis  should  be  added  to  thyroid 
feeding.  In  melancholia,  when  the  mean  blood  pressure 
is  often  very  high,  thyroid  is  a  valuable  accessory  to  the 
opium  treatment. 

When  the  acute  stage  of  the  disease  is  past,  the  diges- 
tion and  appetite  improved  and  the  elimination  sufficient, 
thyroid  in  small  doses  is  very  useful,  increasing  the 
amount  of  the  circulation  and  consequently  the  nutrition 
of  the  organs,  patients  often  gaining  weight  during  its  use. 

Puerperal  insanity  is  probably  the  most  uniformly  bene- 
fited, the  reason  being  that  the  thyroid  has  suffered  from 
hypersecretion  during  pregnancy  and  is  suffering  from 
cell  fatigue,  but  hypothyroidea  is  certainly  not  the  cause 
of  puerperal  insanity  or  at  least  only  in  very  rare  cases. 

It  would  seem  probable  that  the  thyroid  would  act  as 
an  hypnotic  from  its  action  upon  the  blood  vessels,  re- 
ducing the  bulk  of  blood  passing  through  the  brain ;  in  the 
ordinary  sense,  viz:  that  a  dose  at  bedtime  will  produce 
Sleep,  it  certainly  is  neither  a  hypnotic  nor  an  anodyne, 


MENTAL    DISEASES.  251 

but  often  the  addition  of  a  small  dose  of  thyroid  to  the 
daily  medicine  will  in  a  few  days  render  the  nse  of  a  hyp- 
notic unnecessary.  Here  again  the  indications  for  its  use 
must  be  looked  for. 

There  are  some  cases  of  delusional  insanity  which  seem 
to  be  entirely  due  to  thyroid  insufficiency ;  for  example,  a 
young  woman  of  about  28  years  of  age,  in  the  practice 
of  Dr.  MacCalman,  complained  of  visions  of  "seeing  the 
dead"  at  night.  This  delusion  occurred  once  or  twice  a 
month  and  was  so  vivid  that  she  would  scream  and  run  to 
another  room  for  protection,  leaving  her  in  a  very  nervous 
condition.  She  could  give  no  very  clear  account  of  any 
disease  before  puberty,  but  stated  that  she  had  not  men- 
struated until  her  twentieth  year,  having  had  scanty  and 
at  times  painful  periods  all  her  life.  Her  hair  fell  out  at 
irregular  intervals,  her  mean  pressure  was  high;  her  thy- 
roid gland  could  be  palpated  and  was  evidently  enlarged, 
feeling  hard  to  the  touch.  On  these  symptoms  she  was 
prescribed  thyroid.  During  the  first  month  of  treatment 
she  had  one  vision,  her  menstruation  was  free  and  normal 
and  she  had  no  more  visions  for  some  time  while  taking 
six  grains  a  day.  She  stopped  the  treatment  and  the 
visions  returned,  disappearing  again  on  resuming  treat- 
ment. 

In  the  administration  of  thyroid  there  are  several  points 
which  are  of  great  importance:  the  initial  dose  should 
nearly  always  be  small,  one  grain  three  times  a  day  is,  as 
.a  rule,  safe  and  can  be  gradually  increased,  but  it  is  very 
rarely  necessary  to  go  above  two  grains.  Another  point 
is  the  condition  of  the  digestive  tract,  as  thyroglobulin  is 
precipitated  by  organic  and  inorganic  acids,  it  is  impor- 
tant that  alkalis  should  be  administered  at  the  same  time, 
as  should  the  intestines  contain  large  quantities  of  organic 
acids,  a  by  no  means  uncommon  condition,  the  drug  will 
be  only  partially  absorbed.      The  condition  of  the  heart 


252  THE    THYROID    AND    PARATHYROID    GLANDS. 

requires  watching,  as  an  overdose  may  produce  serious 
results  and  very  great  depression  of  spirits ;  especial  care 
is  required  in  old  people  where  atheromatous  arteries  and 
fatty  heart  may  exist.  Of  the  drugs  which  are  advan- 
tageously combined  with  the  thyroid  arsenious  acid  is 
generally  indicated  and  appears  to  aid  the  treatment. 
Strychnia,  digitalis  and  adonis  vernalis,  especially  the  lat- 
ter, are  of  benefit  when  the  heart  is  weak  and  the  dilata- 
tion marked.  Opium  in  nervous  diseases  gives  better  re- 
sults in  many  cases  when  combined  with  thyroid,  the  latter 
counteracting  the  tendency  of  the  opium  to  contract  the 
arterioles. 

Thyroid  treatment  is  no  universal  panacea  for  every  ill 
that  flesh  is  heir  to,  but  bearing  in  mind  its  physiologic 
action  and  seeking  for  the  indications  for  its  use  it  is  un- 
doubtedly a  valuable  therapeutic  aid. 

THE    THYEOID   DURING   PETAL   LIEE. 

In  the  sixth  week  of  intrauterine  life  the  organs  of  the 
thorax  and  upper  part  of  the  abdomen  may  be  said  to' 
have  completed  their  development;  that  is  to  say,  they 
grow  during  the  remaining  34  weeks  but  show  no  changes 
in  construction  till  birth  forces  new  functions  upon  them. 
At  this  period  the  development  of  the  thymus  from  the 
entoderm  of  the  third  gill  cleft  has  begun,  the  two  lateral 
anlages  of  the  thyroid  unite  with  the  single  median  anlage 
at  the  seventh  week,  the  ductus  thyroglossus  may  remain 
open  till  the  eighth  week  while  hollow  acini  have  com- 
menced to  form. 

At  birth  the  isthmus  of  the  thyroid  gland  lies  in  front  of 
the  trachea,  opposite  the  body  of  the  fifth  and  sixth  verte- 
brae; with  the  head  flexed  it  is  in  contact  with  the  upper 
border  of  thymus,  its  lateral  lobes  extending  from  the 
lower  border  of  the  thyroid  cartilage  to  the  level  of  the 
fourth  or  fifth  tracheal  ring.     The  weight  of  the  gland  is 


THE    THYEOID    DUKHSTG    FETAL,    LIFE.  253 

given  by  Ballentyne  as  7  grms.  The  writer  has  found  the 
average  weight  in  two  stillborn  children  at  term  to  be  only 
1.4  grms. ;  other  writers  place  the  average  weight  at  about 
2  grms. 

The  thyroid  is  known  to  be  the  great  regulator  of  body 
metabolism  and  to  be  essential  for  growth ;  in  at  any  rate 
the  early  years  of  life  defects  in  it  are  the  cause  of  cretin- 
ism and  infantilism,  diminished  thyroid  activity  leading 
to  a  decrease  of  the  nutritive  processes.  The  thyroid 
function  is  increased  during  pregnancy  and  also  during 
lactation,  the  marked  flow  of  milk  on  the  third  day  of  the 
puerperium  is  due  to  the  increase  of  the  thyroid  secretion 
in  the  maternal  blood  caused  by  the  birth  of  the  fetus. 
Experimentally  it  has  been  shown  as  stated  in  a  previous 
chapter,  that  the  administration  of  thyroid  increases  the 
secretion  of  milk.  The  question  arises, Has  the  thyroid  of 
the  fetus  the  same  regulating  function  in  connection  with 
the  metabolism  of  antenatal  life  as  the  thyroid  of  the 
mother  over  adult  life,  or  has  the  thyroid  of  the  mother 
the  double  function  of  regulating  both  the  maternal  and 
the  fetal  metabolic  processes  1  It  has  been  shown  by  ex- 
periment, as  stated  in  a  previous  chapter,  that  if  the  thy- 
roid of  the  mother  be  removed  there  is  apparently  a  com- 
pensating hypertrophy  of  the  thyroid  of  the  fetus ;  it  has 
further  been  shown  that  the  fetal  thyroid  contains  no 
iodin  and  in  a  number  of  cases  that  I  have  examined  of 
stillborn  children  at  term  and  also  of  children  who  have 
lived  a  few  weeks  that  there  is  no  iodin  in  the  gland.  The 
fetal  gland  contains  thyromucin,  but  it  does  not  contain 
the  substance  which  quickens  the  pulse  and  lowers  the 
blood  pressure.  "Whatever  may  be  the  function  of  the 
fetal  thyroid  during  fetal  life  it  is  evident  that  it  is  from 
the  maternal  gland  that  the  fetus  receives  the  active 
principle,  and  further  that  as  the  child  at  birth  and  for 
some  time  after  has  no  thyroidin  in  the  thyroid  it  must 


254 


THE    THYEOID    AND    PAEATHYEOID    GLANDS. 


receive  the  amount  which  it  requires  from  the  mother 
through  the  milk.  In  the  cow  it  is  otherwise ;  the  gland 
of  the  fetal  calf  contains  iodin  as  well  as  the  substance 
which  increases  the  pulse  rate  and  reduces  the  blood  pres- 
sure. It  seems  probable  that  under  these  circumstances 
that  cow's  milk  will  not  contain  any  thyroidin  while  hu- 
man milk  will  contain  it. 

It  seems  possible  that  the  difficulty  of  rearing  infants 
on  artificial  food  may  be  due  to  the  absence  of  thyroidin 
in  the  cow's  milk. 

Quantitative  analyses  of  the  thyroids  for  iodin  and 
thyrogiobulin  were  made  of  six  children  dying  of  inani- 
tion. In  no  case  was  any  iodin  found  in  the  gland  and 
the  amount  of  thyrogiobulin  estimated  by  Oswald's  method 
gave  the  following  results : 


Children  Dying  of  Inanition. 

Normal  Children 

Weight  of 

Thyrogiob- 

Weight of 

Thoroglob- 

Thyroid. 

ulin. 

Iodin. 

Thyroid. 

ulin. 

Iodin. 

1.4 

0.0912 

absent 

1.9 

0.4686 

trace 

1.4 

0.0882 

u 

(2  yrs.  old) 

0.64 

0.0574 

" 

1.3 

0.1083 

absent 

0.9 

0.084 

a 

(stillborn) 

1.45 

0.089 

et 

1.4 

0.1029 

u 

0.7 

0.035 

" 

( stillborn ) 

The  above  analyses  show  that  in  children  dying  of  inani- 
tion the  weight  of  the  thyroid  is  but  slightly  lower  than  in 
stillborn  children,  while  the  thyrogiobulin  is  less,  and  that 
iodin  is  absent  both  in  the  inanition  cases  and  in  stillborn 
children. 


BIBLIOGRAPHY. 


Owing  to  the  very  large  amount  of  literature  on  the  subject  of  the 
thyroid  and  parathyroid  glands  only  articles  published  since  1900  are 
indexed;  for  earlier  publications  the  reader  is  referred  to  the  Catalogue 
of  the  Surgeon-General's  Library,  Washington,  D.  C. 

Achar    (G.)  :   XIII  Congres  Internat.  de  Med.,  Paris,  1900. 

Apert  (E.):  Bulletin  Medical,  1901.  Arch,  de  Med.  des  Enfants,  1902. 
Bulletin  de  la  Soc.  de  Pediatrie  de  Paris,  1901.  C.  R.  de  la  Soeiete 
de  Biologie,  Paris,  1902.  Annales  de  Medecine  et  Chirurgie  Infan- 
cies, 1902. 

Actualities  Mgdec,  1902. 

Ausset    (E.)  :   Congres  Periodique  de  Gyn.,  d'Obstet.  et  de  Pediatrie,  1901. 

Azoulay  (L.)  :  Presse  Medicale,  1900. 

Baldi:   II  Morgagni,  1900. 

Baldoni:  R.  Accademia  Med.  di  Roma,  1900. 

Ball  (V.)  :  Soc.  de  Biol.,  1902. 

Bassal:  These,  Toulouse,  1900-1901. 

Belfrage:   Hygeia,  1900. 

Bertarelli:   Gazz.  degli  Osped.,  1900.     Revue  Gen.  de  Path.  Interne,  1901. 

Bezy:  XIII  Congres  Internat.  de  Med.,  Paris,  1900. 

Blum:  Die  schildruse  als  entgiftendes  organ,  1899.  Virchow's  Archiv, 
clviii.      Jour,  de  physiol.  et  pathol.  gen.,  1900. 

Blumreich  et  Zunte:  Arch.  f.  gyn.,  1902. 

Bourcet    (P.)  :  These,  Paris,  1900. 

Bourneville:  Traite  de  Medecine  et  de  Therapeutique,  1902. 

Bourneville  et  Laurens:  Progres  Medical,  1901. 

Braoude  (Mile.  Nehama)  :  These,  Paris,  1901. 

Breton:   These,  Lille,  1901-1902. 

Briquet:  Presse  Medicale,  1902. 

Callari:  Gazzetta  degli  Ospedali  e  delle  Cliniche,  1901.  Riforma  Medica, 
1901. 

Cao:  Jour,  des  Maladies  Cutanees  Syphilitiques,  1900.  Riforma  Medica, 
1900. 

Cardile  et  Fiorentini:  R.  Accad.  Peloritana  di  Messina,  1900. 

Carrel:  Gaz.  des  Hopitaux,  1900. 

Carrel-Billard :  These,  Lyon,  1900. 

Caseli:  Rivista  Sperimentale  di  Freniatria  e  Med.  Leg.  d  Alien,  1900. 
Lyon  Medical,  1900. 

Cecca:   Soc.  Medico-Chirurg.  de  Boulogne,  1902. 

Chantemesse  et  Podvvyssotsky :  Les  Processus  Generaux,  1901. 

Charrin  et  Bourcet:   Soc.  de  Biol.,  1900. 

Chatin  et  Gurnard:  Lyon  Medical  1900. 

255 


256  THE    THYROID    AND    PARATHYROID    GLANDS. 

Chepault:   Soc.  cle  Pediatric,  1902.      Gaz.  Hebd.  de  Med.  et  de  Chirurgie, 

1902. 
Cristiani:   Soc.  de  Biol.,  1900.       Progres  Medical,  1901. 
Cyon    (de)  :  Rev.  Gen.  des  sc.  Pures  et  Appliquees,  1901. 
Dalche:  Bulletin  de  la  Soc.  Med.  des  Hopitaux  de  Paris,  1901.      Soc.  Med. 

des  Hopitaux,  1901.      Sem.  MeU,  1901. 
Debove:  Presse  Medicale,  1901. 
Dezon:   Revue  Hebdomadaire  de  Laryngologie,  d'Otologie  et  de  Rhinologie, 

1901. 
Dupre  et  Guillain :  Bullet,  de  la  Soc.  Med.,  des  Hopitaux,  1900. 
Easterbrook:   The  Scot.  Med.   and  Surg.  Jour.,   1901. 
Ferrannini:   Congres  de  la  Soc.  Ital.  de  Med.  Interne,  Rome,  1901. 
Fraissex:  These,  Paris,  1900. 

Fruhinsholz  et  Jeandelize:   Presse  Medicale,  1902. 
Gamier:  Province  Medicale,  1900. 

Gautier   (A.)  :   Acad,  de  Med.,  1900.      Bull.  Acad,  de  Med.,  1900. 
Gautier    (Ch.)  :   These,  Lyon,   1900. 
Gley:  British  Med.  Jour.,  1901. 
Glynn:  Liverpool  Med.  Soc,  1900. 
Hallion:   Arch.  Gen.  de  Med.,  1901. 
Haushalter  et  Guerin:   Revue  Mensuelle  des  Maladies  de  l'Enfance,   1902. 

Soc.   de  Med.  de  Nancy,   1902.      Rev.  Med.   de  l'Est.,   1902.      Soc.   de 

Biol.,  1902. 
Herrgott:   Soc.  Med.  de  Nancy,  1902.      Rev.  Med.  de  l'Est.,  1902. 
Hertoghe:   Nouvelle  Iconographie  de  la  Saltpetriere,  1900. 
Hutinel:  Gaz.  Heb.  de  Med.  et  de  Chirur.,  1902. 
Jacquemet:   These,  Montpellier,  1900. 
Joachimstal:  Deutsche  med.  Woch.,  1900. 
Kashiwamura:   Arch.  f.  pathol.  Anat.  u.  Physiol.,   1901. 
Katzenstein:  Deutsche  med.  Woch.,  1900. 
Krafft  Ebing:  Bolletino  delle  Cliniche,  1900. 
Lannois:  Nouvelle  Iconographie  de  la  Saltpetriere,  1900-1901. 
Leblanc:  Soc.  de  Biol.,  1902. 
Lusena :  Riforma  Medica,  1900. 

Marie:  Soc.  Med.  des  Hop.,  1902.      Sem.  Med.,  1902. 
Mayet    (L.)  :   Lyon  Medical,   1900.      Arch.  General  de  Med.,   1900.      Bull. 

et  Mem.  de  la  Soc.  d' Anthropologic  de  Paris,  1901. 
Meige  et  Allard:   Soc.  de  Neurol,  de  Paris,  1900. 
Murray:  Diseases  of  the  Thyroid  Gland,  1902. 
Nicholson:   The  Scot.  Med.  and  Surg.  Jour.,  1901. 
Patel:  Gaz.  Hebd.  de  Med.  et  de  Chir.,  1901. 
Peckranz:   Neurol.  Centrallbl.  Biol.,  1899. 
Pollosson  et  Genevet:   Lyon  Med.,  1901. 
Ponfick:  Deutsche  med.  Woch.,  1900. 
Porges:  Berl.  klin.  Woch.,  1900. 
Pornain:   Progres  Medical,  1900. 
Quincke:  Deutsche  med.  Woch.,  1900. 
Richardiere:  Soc.  de  Pediatrie,  1902. 
Riviere:  Lyon  Med.,  1900-1901. 
Roger  et  Gamier:  Presse  Medicale.      Soc.  de  Biol.,  1901. 


BIBLIOGRAPHY.  257 

Roux  et  Vitaul :   Revue  Neurol.,  1901. 

Rummo:  Riforma  Medica,  1900. 

Sainton  et  Ferraud:   Bull,  de  la  Soc.  Med.  des  Hop.  de  Paris,   1901. 

Scheffmacher:  Deutsche  Archiv  f.  klin.  Med.,  1901. 

Siegert:   Arch,  de  Me.  des  Enfants,  1900.     Jahrbuch  f.  Kinderheilk.,  1901. 

Thomas:  Revue  Hebdom.  et  Laryng.,  d'Otol.  et  Rhinol.,  1900. 

Torri:  Suppl.  al  Pcliclinico,  1900. 

Ulrich:   Nordiskt  mediunskt  Archiv,   1900. 

Verriest :   Belgique  Medicale,   1900. 

Ziegler:  Lehrbuch  der  Allgemeinen  und  speciellen  pathol.  Anat.,  1901. 


INDEX. 


Abnormalities  of  thyroid,   10 
Accessory  thyroid,  13 
Achondroplasia,   180 
Acute  thyroiditis,   129 

suppurative,   131 

gangrenous,  132 

rheumatismal,-.  132 

mumps,    132 

grippe,   133 

malaria,  133 

typhoid,  133 

pyemia,  133 
Adiposis    dolorosa,   248 
Anatomy,  thyroid,  8 

parathyroid,   17 
Analysis,  methods   of,   57 
Anangioplasia,  173 
Anesthesia,   107 
Anthrax,  126 
Aorta,   44 
Arsenic,  68 
Ateleiosis,  175 

B 

Basedow's  disease,  197 

blood  pressure,  227 

insanity  in,  218 

incomplete,  226 

pathology,  223 

symptoms,  203,  209 

serum  treatment,  230 

skin  pigmentation,  219 

treatment,  228 

urine,    222,    226 
Blood  changes  after  thyroidectomy. 

26,  49 
Bone  marrow,  extract  of,  5 
Brain,  desiccated,  6 
Bright's  disease,  237 
Bromin  in  thyroid,  08 


C 
Cancer,  140 

Cachexia   strumipriva,   1  IS 
Castratos,  2 
Chemistry,   56 

Complications,   surgical,   104,   106 
Congestion,    121 

pathologic  anatomy,   122 
Cretinism,    144 

in  animals,  161 

parathyroids   in,    153 

pathology,  154 

symptoms,  155 
Cystic  goitre,  90 
Cysts,  surgery  of,  113 

I) 

Dangers  of  operation,  100,  103,  107 
Desiccated  brain,  6 
Development  of  thyroid,  39 
Dibromostearic  acid,  68 
Diphtheria,  125 

toxin,  injection  of,  127 

E 
Eclampsia,  241 
Embryology,   8 
Emergency  operation,  100 
Enucleation,  110 
Epilepsy,  237 
Extirpation  of  thyroid,  23 

of  parathyroid,  29,  34,  37 
Extracts  of  bone  marrow,  5 

kidney,  7 

liver,  6,   7 

lymphatic  glands,   7 

ovaries,  3 

parotid  gland,  5 

pituitary  body,   5 

prostate  gland,  7 

spleen,  5 

suprarenal,  7 


259 


260 


INDEX. 


Extracts  of  testicles,  2 
thymus.   4 


Feeding  thyroid.   35 

influence    after    thyroidectomy, 
55 
Fetal  thyroid,  functions  of,  252 
Functions  of  thyroid,  21,  69,  72 

parathyroid,  33,  72 

Notkin's  theory.   69 

antitoxic  theory,  70 

G 

Gangrene,    132 
Geromorphine  cutanee,  180 
Glycocholate  of  soda,  6 
Glycosuria,  235 
Goitre,  endemic,  73 

anatomy,  81 

congenita],  79 

distribution  of,  74 

etiology  of,  76 

experimental  production  of,  77 

infection    theory,    79 

follicular  goitre,  86 

struma  vasculosa,  87,  95 

struma  fibrosa,  88,  95 

symptomatology,  S9 

struma  parenchymatosa,  94 

struma  colloide,  95 

mixed   goitre,    95 

thyroid  feeding  in,  98 

thymus  feeding  in,  98 

iodin  in,   9S 

sporadic,   80 
Grippe,  133 

H 
Heart,     effect     of     thyroid     feeding 

on,   49 
Hemorrhages,  105,  248 
Historical,    1 
Histology,  thyroid,  14 

parathyroid,   17 
Hydatid  cysts,   142 
Hypophyses  cerebri,  53 


Infantilism,  myxedematous,  164 

etiology,  165 

non-myxedematous.  174 

symptoms,   165 

type  Loraine,   169 
Infectious  diseases,  121 
Inoculation  experiments,  126 
Iodin,  57,  59,  64 
Impotence,  245 

Insanity  in  Basedow's  disease,  218 
Isthmus,  removal  of,  111 


K 


Kidney,  7 


Lactation,  43 
Ligature  of  arteries,  112 
Liver,  7 
Lymphatics,  12 

M 

Malignant  diseases  of  thyroid,  112 

Malaria,  133 

Measles,  125 

Menstrual  disturbances,  238 

Metabolism  experiments,  44 

Menstruation,  41 

Mental  disease,  248 

Mucin,  8 

Mumps,  132 

Myxedema,  1S3 

incomplete,  1S9 

production  of,  33 

symptom,  183 

treatment,   196 

urine,   189 

X 

Nerves,  28,  35 
Nervous  diseases,  246 
Nitrogen  metabolism,  46 

0 
Obesity,  234 

Organs  of  generation,  41 
Oxydase,   07 
Oxygen,  metabolism  of,  45 


INDEX. 


261 


Parathyroids,   anatomy,   17 

histology,  17 

cretinism,  153 

infectious  diseases,  124 
Paralysis  agitans,  247 
Parotid  gland,  G 
Pituitary  body,  5 
Pneumococcus,  126 
Precocious  development,  179 
Pregnancy,  42 
Progeria,   179 
Prostate,   7 
Puberty,   42 
Pyemia,  133 

R 
Eheumatismal  thyroiditis,  132 

S 
Sarcoma,   142 
Scarlet  fever,   125 
Senilism,   178,  236 
Skin  in  Basedow's  disease,  226 

diseases  of,  247 
Smallpox.  125 
Splenic  extract,  5 
Spermin,   3 

Suppurative  thyroiditis,  127-131 
Sulphur,   66 

Surgery,    indications    for   operation, 
100 

emergency  operation,  100 

tracheotomy,  101 

dangers  of,   101-103,   107 

statistics  of,  104,  114 

complications,     104,     106,    115, 
US 


Surgery,  hemorrhage,  105 

anesthesia,  107 

preparation,  107 

technique,  108 

enucleation,  110 

isthmus,  removal  of,  111 

malignant  disease,   112 

ligature  of  arteries,  112 

cysts,   113 

wounds,  119 
Syphilis,  139 


Temperature     after     thyroidectomy. 

54 
Tetanus  toxin,  127 
Tetany,    115,   239 
Thymus  gland,  4 
Thyroidismus,  48 
Thyroid  feeding,  45,  48,  49 
Thyroglobulin,  58 
Thyroantitoxin,  56 
Tracheotomy,   101 
Tuberculosis,  134 
Typhoid  bacillus,  126-133 
Type  Loraine,  169 

U 

Urine  after  thyroidectomy,  54 
in  myxedema,    189 
Basedow's  disease,  226 


Veins,  12 


V 


w 


Weight  of  thyroid,  11 
Wounds,  surgery  of,  119 


DATE  DUE 

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